Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).
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Session Overview |
| Date: Saturday, 10/June/2023 | |
| 9:00am - 6:00pm | Young Investigators Meeting Registration and Information Desk Location: Bologna Congress Center |
| 10:00am - 6:00pm | Young Investigators Meeting Location: Bologna Congress Center - Sala Italia To see the full programme of this Meeting, visit our website on this page. |
| Date: Sunday, 11/June/2023 | |
| 10:00am - 6:00pm | Slides Center Location: Slides Center |
| 10:00am - 6:00pm | Registration Desk Location: Bologna Congress Center |
| 11:00am - 1:00pm | E-MIT Assembly Location: Bologna Congress Center - Sala Europa |
| 1:00pm - 2:00pm | Lunch Location: Bologna Congress Center - Sala Europa |
| 2:30pm - 3:00pm | Opening Ceremony Location: Bologna Congress Center - Sala Europa |
| 3:00pm - 3:45pm | Keynote Lecture: Doug Turnbull Location: Bologna Congress Center - Sala Europa |
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Invited
ID: 676 Invited Speakers Mitochondrial disease: past successes and future challenges Newcastle University, United Kingdom |
| 3:45pm - 4:00pm | Coffee Break Location: Bologna Congress Center |
| 4:00pm - 5:30pm | Session 1.1: The impact of mtDNA variation and environment on rare and common diseases Location: Bologna Congress Center - Sala Europa Session Chair: Ian Holt Session Chair: Emanuela Bottani Invited Speakers: P. Chinnery; A. Enriquez |
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Invited
ID: 679 Invited Speakers The role of mtDNA variation in common and rare diseases Cambridge-UK, United Kingdom Invited
ID: 2107 Invited Speakers How mtDNA can talk with the complex landscape of nuclear encoded OXPHOS information? Spanish National Center for Cardiovascular Research (CNIC) Oral presentation
ID: 369 The impact of mtDNA variation and environment on rare and common diseases Understanding the pathophysiological mechanisms of mitochondrial diseases with MITOMICS through an integrated multi-OMICS approach of Mitomatcher, the French mitochondrial disease database 1Université Côte d’Azur, INSERM U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice, France; 2Département de Génétique, UMR CNRS 6015 INSERM 1083, CHU et Université d’Angers, Angers, France; 3Réseau français des laboratoires de diagnostic pour les maladies mitochondriales (Bordeaux, Caen, Grenoble, Lille, Lyon, Le Kremlin-Bicêtre, Pitié Salpêtrière, Necker Enfants Malades, Reims), Centres de référence pour les maladies mitochondriales (CALISSON, CARAMMEL), France; 4Université de Nantes, Nantes, France; 5Université Côte d’Azur, MDLab, Nice, France; 6Filière FILNEMUS, CHU La Timone, Marseille, France; 7INRIA, Equipe EPIONE, Nice, France; 8University of Leicester, Dept.Genetics, UK Oral presentation
ID: 570 The impact of mtDNA variation and environment on rare and common diseases Generating a complete human panmitogenome 1The Rockefeller University, United States of America; 2Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy; 3Medical University of Innsbruck, 6020 Innsbruck, Austria; 4Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA; 5Medical University of Innsbruck, 6020 Innsbruck, Austria; 6Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40139 Bologna, Italy; 7IRCCS Institute of Neurological Sciences of Bologna; 8Forensic Science Program, The Pennsylvania State University, University Park, PA, USA Oral presentation
ID: 479 The impact of mtDNA variation and environment on rare and common diseases Negative selection of mitochondrial DNA mutations in the blood 1Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne; 2The Human Dendritic Cell Lab, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne; 3NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne; 4Equal Contributions; 5Equal Contributions Flash Talk
ID: 329 The impact of mtDNA variation and environment on rare and common diseases Parsing universal heteroplasmy in a large maternal lineage carrying the common LHON variant m.11778G>A/MT-ND4 1Azienda USL di Bologna - IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 3Istituto Italiano di Tecnologia – IIT, Genova, Italy; 4Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil; 5Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; 6Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 7Medical Research Council Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK Flash Talk
ID: 441 The impact of mtDNA variation and environment on rare and common diseases PNPLA3, MBOAT7 and TM6SF2 modify mitochondrial dynamics in NAFLD patients: dissecting the role of cell-free circulating mtDNA and copy number 1Fondazione IRCCS Cà Granda Ospedale Policlinico, Italy; 2Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 3Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy |
| 5:30pm - 6:15pm | Show Location: Bologna Congress Center - Sala Europa |
| 6:15pm - 7:00pm | Transfer to Cocktail Venue Location: Bologna Congress Center - Sala Europa |
| 7:00pm - 10:00pm | Welcome cocktail Location: Palazzo Isolani |
| Date: Monday, 12/June/2023 | |
| 8:00am - 6:30pm | Slides Center Location: Slides Center |
| 8:00am - 6:30pm | Registration Desk Location: Bologna Congress Center |
| 9:00am - 10:45am | Session 2.1: mtDNA maintenance and expression Location: Bologna Congress Center - Sala Europa Session Chair: Zofia Chrzanowska-Lightowers Session Chair: Massimo Zeviani Invited Speakers:
M. Falkemberg; A. Filipovska |
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Invited
ID: 236 Invited Speakers Initiation of mitochondrial DNA replication in mammalian cells. Gothenburg University, Sweden Bibliography
Maria Falkenberg defended her Ph.D. thesis (2000) at the University of Gothenburg, Sweden, after spending three years as a visiting student with Prof. I.R. Lehman, Stanford University School of Medicine. After postdoctoral work with Prof. Nils-Göran Larsson (2001-2002), she was appointed assistant professor at the Karolinska Institutet (2003). Since 2011, she is professor of medical biochemistry at the University of Gothenburg. The Falkenberg laboratory studies DNA replication in mammalian mitochondria, using in-vitro biochemistry, structural biology and and cell biology to study the underlying enzymatic processes. The laboratory also investigates the molecular consequences of disease-causing mutations affecting mitochondrial DNA replication and develops new, rational therapeutic approaches. Invited
ID: 680 Invited Speakers Regulation of mitochondrial gene expression in disease University of Western Australia, Australia Oral presentation
ID: 423 mtDNA maintenance and expression Mitochondrial translation termination at non-canonical stop codons 1Karolinska Institutet, Stockholm, Sweden; 2University of Pennsylvania, Pennsylvania, USA; 3Max-Planck-Institute for Biology of Ageing, Cologne, Germany Bibliography
Krüger A, Remes C, Shiriaev DI, Liu Y, Spåhr H, Wibom R, Atanassov I, Nguyen MD, Cooperman BS, Rorbach J. Human mitochondria require mtRF1 for translation termination at non-canonical stop codons. Nat Commun 14, 30 (2023). Oral presentation
ID: 268 mtDNA maintenance and expression Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability 1Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden; 2Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 3Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 4Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK; 5The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 6North East and Yorkshire Genomic Laboratory Hub, Central Lab, St. James's University Hospital, Leeds, UK; 7Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK; 8Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 9NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK; 10Nuffield Department of Women’s & Reproductive Health, The Women's Centre, University of Oxford, Oxford, UK; 11Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; 12Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; 13Department of Internal Medicine, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil; 14Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil; 15Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA; 16Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA; 17The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel; 18The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; 19The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 20Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Israel; 21Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; 22Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden Bibliography
Menger et al. (2022). Two type I topoisomerases maintain DNA topology in human mitochondria. Nucleic Acids Research; 50(19):11154-11174. Tan et al. (2022). The human mitochondrial genome contains a second light strand promoter. Molecular Cell; 82(19): 3646-3660. Misic et al. (2022). Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Research; 50(15): 8749-8766. Menger et al. (2021). Controlling the topology of mammalian mitochondrial DNA. Open Biology; 11(9): 210168. Jiang et al. (2021). The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication. Science Advances; 7(27): eabf8631. Oral presentation
ID: 244 mtDNA maintenance and expression The role of replicative exonucleases in mitochondrial DNA replication and degradation University of Miami Miller School of Medicine, United States of America Bibliography
S27 of IFNα1 Contributes to Its Low Affinity for IFNAR2 and Weak Antiviral Activity Nikunj Sharma, Anya J. O'Neal, Christian Gonzalez, Megen Wittling, Erisa Gjinaj, Lisa M. Parsons, Debasis Panda, Alexey Khalenkov, Dorothy Scott, Saurav Misra, and Ronald L. Rabin Journal of Interferon & Cytokine Research 2019 39:5, 283-292 Flash Talk
ID: 127 mtDNA maintenance and expression Processing of mitochondrial RNA in health and disease: the role of FASTKD5. 1The Neuro & McGill University, Montreal, Quebec, Canada; 2Dell School of Medicine, University of Texas at Austin, Austin, TX, USA Bibliography
1.Arguello T, Peralta S, Antonicka H, Gaidosh G, Diaz F, Tu YT, Garcia S, Shiekhattar R, Barrientos A, Moraes CT. (2021) ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly. Cell Rep. 2021 Dec 21;37(12):110139. doi: 10.1016/j.celrep.2021.110139. 2.Go CD, Knight JDR, Rajasekharan A, Rathod B, Hesketh GG, Abe KT, Youn JY, Samavarchi-Tehrani P, Zhang H, Zhu LY, Popiel E, Lambert JP, Coyaud É, Cheung SWT, Rajendran D, Wong CJ, Antonicka H, Pelletier L, Palazzo AF, Shoubridge EA, Raught B, Gingras AC. (2021) A proximity-dependent biotinylation map of a human cell. Nature. 2021 Jul;595(7865):120-124. doi: 10.1038/s41586-021-03592-2. 3.Antonicka H, Lin ZY, Janer A, Aaltonen MJ, Weraarpachai W, Gingras AC, Shoubridge EA. (2020) A High-Density Human Mitochondrial Proximity Interaction Network. Cell Metab. 2020 Sep 1;32(3):479-497.e9. doi: 10.1016/j.cmet.2020.07.017. 4.Maiti P, Antonicka H, Gingras AC, Shoubridge EA, Barrientos A. (2020) Human GTPBP5 (MTG2) fuels mitoribosome large subunit maturation by facilitating 16S rRNA methylation. Nucleic Acids Res. 2020 Aug 20;48(14):7924-7943. doi: 10.1093/nar/gkaa592. 5.Antonicka H, Choquet K, Lin ZY, Gingras AC, Kleinman CL, Shoubridge EA. (2017) A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep. 2017 Jan;18(1):28-38. doi: 10.15252/embr.201643391. Flash Talk
ID: 524 mtDNA maintenance and expression Mechanisms of mtDNA maintenance and segregation in the female germline 1Karolinska Institutet, Stockholm, Sweden; 2MRC Mitochondrial Biology Unit, Cambridge, United Kingdom; 3Department of Clinical Neurosciences, University of Cambridge, United Kingdom Flash Talk
ID: 116 mtDNA maintenance and expression The human Mitochondrial mRNA Structurome reveals Mechanisms of Gene Expression in Physiology and Pathology 1University of Miami, United States of America; 2Harvard Medical School, United States of America Bibliography
1- Structural basis of LRPPRC-SLIRP-1 dependent translation by the mitoribosome. Vivek Singh, J. Conor Moran, Yuzuru Itoh, Iliana C. Soto, Flavia Fontanesi, Mary Couvillion, Martijn A. Huynen4, Stirling Churchman, Antoni Barrientos*, Alexey Amunts*. Nat Struct Mol Bill. 2023 (in press) 2-Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors. Timón-Gómez A, Scharr AL, Wong NY, Ni E, Roy A, Liu M, Chau J, Lampert JL, Hireed H, Kim NS, Jan M, Gupta AR, Day RW, Gardner JM, Wilson RJA, Barrientos A, Chang AJ. Elife. 2022 Oct 18;11:e78915. doi: 10.7554/eLife.78915. 2- Coordination of metal center biogenesis in human cytochrome c oxidase. Nývltová E, Dietz JV, Seravalli J, Khalimonchuk O, Barrientos A. Nat Commun. 2022 Jun 24;13(1):3615. doi: 10.1038/s41467-022-31413-1. |
| 10:45am - 11:00am | Coffee Break Location: Bologna Congress Center |
| 11:00am - 12:45pm | Session 2.2: Clinical 1: from new genes to old and novel phenotypes Location: Bologna Congress Center - Sala Europa Session Chair: Agnes Rotig Session Chair: Daniele Ghezzi Invited Speakers: R. Horvath; H. Prokisch |
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Invited
ID: 672 Invited Speakers The role of mitochondria in neuromuscular diseases Cambridge-UK, United Kingdom Bibliography
Van Haute L, et al. Nat Commun 2023 Feb 23;14(1):1009 Invited
ID: 696 Invited Speakers Innovative approaches for the molecular diagnosis of mitochondrial disorders Technical University Munich Institute of Human Genetics Oral presentation
ID: 615 Clinical 1: from new genes to old and novel phenotypes Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK; 4Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 5Department of Neurosciences, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 6Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 7National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, London, UK; 8Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK; 9Genomics England, One Canada Square London, UK Bibliography
(1) Riley L.G. et al, The diagnostic utility of genome sequencing in a pediatric cohort with suspected mitochondrial disease Genet Med, 2020 Jul;22(7):1254-1261. (2) Davis R.L., Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis, Neurology. 2022 Aug 16;99(7):e730-e742. Oral presentation
ID: 553 Clinical 1: from new genes to old and novel phenotypes Biallelic variants in MCAT in an infant with lactic acidosis, lipoylation disorder, and early death 1University Children's Hospital, Paracelsus Medical University, Salzburg, Austria; 2Institute of Human Genetics, University Medical Center Eppendorf, Hamburg, Germany; 3Current address: Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany; 4Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany; 5Amalia Children’s Hospital, Radboudumc, Nijmegen, The Netherlands. Oral presentation
ID: 367 Clinical 1: from new genes to old and novel phenotypes Biallelic PTPMT1 variants impair cardiolipin metabolism and cause mitochondrial myopathy and developmental regression 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge UK; 4Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, Turkey; 5Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 6Neurogenetics Unit, Rare and Inherited Disease Laboratory, North Thames Genomic Laboratory Hub, London, UK; 7Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK; 8Neurometabolic Unit, The National Hospital for Neurology and Neurosurgery, London, UK; 9Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK; NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle University, Newcastle upon Tyne, UK; 10Genomics England, London, UK; 11Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey; 12Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt; 13Department of Inherited Metabolic Disease, Division of Women's and Children's Services, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 14Izmir Biomedicine and Genome Center, Izmir, Turkey; 15Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, Izmir Turkey Flash Talk
ID: 201 Clinical 1: from new genes to old and novel phenotypes Heterozygous missense variants in NUTF2 (nuclear transport factor 2) gene, mapping at the OPA8 locus, cause Dominant Optic Atrophy 1IRCCS - Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica - Bologna (Italy); 2Studio Oculistico d'Azeglio - Bologna (Italy); 3Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele - Milano (Italy); 4Department of Genetics & Genomics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD-UAM) - Madrid (Spain); 5Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII - Madrid (Spain); 6Grupo de investigación traslacional con células iPS, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red (CIBERER) - Madrid (Spain); 7Université d’Angers, MitoLab team, UMR CNRS 6015 - INSERM U1083, Unité MitoVasc - Angers (France); 8Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, Institute of Genetic Diseases, Imagine and Paris Descartes University - Paris (France); 9Departments of Biochemistry and Genetics, University Hospital Angers - Angers (France); 10Molecular Genetics Laboratory, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; 11Depart. of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna - Bologna (Italy) Flash Talk
ID: 348 Clinical 1: from new genes to old and novel phenotypes Southern African paediatric patients with King Denborough syndrome are exclusively associated with an autosomal recessive STAC3 variant: is this a highly prevalent secondary mitochondrial disease in this African population? 1Human Metabolomics, North-West University, Potchefstroom, South Africa; 2Department of Paediatrics, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa; 3Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; 4Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom; 5https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/global-contributor-list Bibliography
Schoonen, M., Smuts, I., Louw, R., Elson, J. L., van Dyk, E., Jonck, L. M., Rodenburg, R. J. T., van der Westhuizen, F. H. (2019). Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease. The Journal of molecular diagnostics 21, 503–513. Meldau, S., Owen, E. P., Khan, K., & Riordan, G. T. (2022). Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings. Journal of clinical pathology 75, 34–38. Reinecke, C. J., Koekemoer, G., van der Westhuizen, F. H., Louw, R., Lindeque, J. Z., Mienie, L. J., Smuts, I. (2012). Metabolomics of urinary organic acids in respiratory chain deficiencies. Metabolomics 8, 264-283. Terburgh, K., Coetzer, J., Lindeque, J. Z., van der Westhuizen, F. H., Louw, R. (2021). Aberrant BCAA and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome. Biochimica et biophysica acta. Molecular basis of disease 1867, 166082. Flash Talk
ID: 428 Clinical 1: from new genes to old and novel phenotypes AK3, adenylate kinase isozyme 3, is a new gene associated with PEO and multiple mtDNA deletions 1Fondazione IRCCS Istituto Neurologico Besta, Italy; 2Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Autonomous University of Barcelona, Barcelona, Spain; 3Centro Sclerosi Multipla, P.O. Binaghi, ASL Cagliari, Italy; 4Technical University of Munich, School of Medicine, Institute of Human Genetics, 81675 Munich, Germany; 5Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Munich, Germany; 6Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy Flash Talk
ID: 411 mtDNA maintenance and expression Guanylate kinase 1 deficiency: a novel and potentially treatable form of mitochondrial DNA depletion/deletions syndrome 1Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; 2Seattle Children’s Hospital, Seattle, WA, USA; 3Section of Inborn Errors of Metabolism-IBC. Department of Biochemistry and Molecular Genetics. Hospital Clinic de Barcelona-IDIBAPS, Barcelona.; 4Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona; 5Muscle Research and Mitochondrial Function Lab, Cellex - IDIBAPS. Faculty of Medicine and Health Science - University of Barcelona (UB), Barcelona.; 6Department of Internal Medicine, Hospital Clínic of Barcelona.; 7Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain.; 8Department of Genome Sciences, University of Washington, Seattle, WA, U.S.A. Bibliography
1DiMauro, S., Schon, E. A., Carelli, V. & Hirano, M. The clinical maze of mitochondrial neurology. Nat Rev Neurol 9, 429-444, doi:10.1038/nrneurol.2013.126 (2013). 2Lopez-Gomez, C., Camara, Y., Hirano, M., Marti, R. & nd, E. W. P. 232nd ENMC international workshop: Recommendations for treatment of mitochondrial DNA maintenance disorders. 16 - 18 June 2017, Heemskerk, The Netherlands. Neuromuscul Disord 32, 609-620, doi:10.1016/j.nmd.2022.05.008 (2022). 3Lane, A. N. & Fan, T. W. Regulation of mammalian nucleotide metabolism and biosynthesis. Nucleic Acids Res 43, 2466-2485, doi:10.1093/nar/gkv047 (2015). 4Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S. & Elpeleg, O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29, 342-344, doi:10.1038/ng751 (2001). 5Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S. & Cohen, N. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29, 337-341, doi:10.1038/ng746 (2001). 6Ostergaard, E., Christensen, E., Kristensen, E., Mogensen, B., Duno, M., Shoubridge, E. A. & Wibrand, F. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet 81, 383-387, doi:10.1086/519222 (2007). 7Besse, A., Wu, P., Bruni, F., Donti, T., Graham, B. H., Craigen, W. J., McFarland, R., Moretti, P., Lalani, S., Scott, K. L., Taylor, R. W. & Bonnen, P. E. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. Cell Metab 21, 417-427, doi:10.1016/j.cmet.2015.02.008 (2015). 8Sommerville, E. W., Dalla Rosa, I., Rosenberg, M. M., Bruni, F., Thompson, K., Rocha, M., Blakely, E. L., He, L., Falkous, G., Schaefer, A. M., Yu-Wai-Man, P., Chinnery, P. F., Hedstrom, L., Spinazzola, A., Taylor, R. W. & Gorman, G. S. Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance. Clin Genet 97, 276-286, doi:10.1111/cge.13652 (2020). 9Shintaku, J., Pernice, W. M., Eyaid, W., Gc, J. B., Brown, Z. P., Juanola-Falgarona, M., Torres-Torronteras, J., Sommerville, E. W., Hellebrekers, D. M., Blakely, E. L., Donaldson, A., van de Laar, I., Leu, C. S., Marti, R., Frank, J., Tanji, K., Koolen, D. A., Rodenburg, R. J., Chinnery, P. F., Smeets, H. J. M., Gorman, G. S., Bonnen, P. E., Taylor, R. W. & Hirano, M. RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J Clin Invest 132, doi:10.1172/JCI145660 (2022). 10Bourdon, A., Minai, L., Serre, V., Jais, J. P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A. & Rotig, A. Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet 39, 776-780, doi:10.1038/ng2040 (2007). 11Khan, N., Shah, P. P., Ban, D., Trigo-Mourino, P., Carneiro, M. G., DeLeeuw, L., Dean, W. L., Trent, J. O., Beverly, L. J., Konrad, M., Lee, D. & Sabo, T. M. Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer. J Biol Chem 294, 11920-11933, doi:10.1074/jbc.RA119.009251 (2019). 12Li, Y., Zhang, Y. & Yan, H. Kinetic and thermodynamic characterizations of yeast guanylate kinase. J Biol Chem 271, 28038-28044, doi:10.1074/jbc.271.45.28038 (1996). 13Agarwal, K. C., Miech, R. P. & Parks, R. E., Jr. Guanylate kinases from human erythrocytes, hog brain, and rat liver. Methods Enzymol 51, 483-490, doi:10.1016/s0076-6879(78)51066-5 (1978). 14Dummer, R., Duvic, M., Scarisbrick, J., Olsen, E. A., Rozati, S., Eggmann, N., Goldinger, S. M., Hutchinson, K., Geskin, L., Illidge, T. M., Giuliano, E., Elder, J. & Kim, Y. H. Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sezary syndrome). Ann Oncol 25, 1807-1812, doi:10.1093/annonc/mdu231 (2014). |
| 12:45pm - 1:45pm | Lunch Location: Bologna Congress Center - Sala Europa |
| 1:45pm - 3:30pm | Session 2.3: Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Location: Bologna Congress Center - Sala Europa Session Chair: Cristina Ugalde Session Chair: Giovanni Manfredi Invited Speaker: E. Fernandez-Vizarra; A. Prigione |
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Invited
ID: 176 Invited Speakers Metabolic adaptations of respiratory chain organization and function 1Department of Biomedical Sciences, University of Padova, Italy; 2Veneto Institute of Molecular Medicine, Padova, Italy Bibliography
1.Fernandez-Vizarra, E., Lopez-Calcerrada, S., Sierra-Magro, A., Perez-Perez, R., Formosa, L.E., Hock, D.H., Illescas, M., Penas, A., Brischigliaro, M., Ding, S., et al. (2022). Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab 34, 1792-1808. 10.1016/j.cmet.2022.09.005. 2.Fernandez-Vizarra, E., and Ugalde, C. (2022). Cooperative assembly of the mitochondrial respiratory chain. Trends Biochem Sci 47, 999-1008. 10.1016/j.tibs.2022.07.005. 3.Fernandez-Vizarra, E., Lopez-Calcerrada, S., Formosa, L.E., Perez-Perez, R., Ding, S., Fearnley, I.M., Arenas, J., Martin, M.A., Zeviani, M., Ryan, M.T., and Ugalde, C. (2021). SILAC-based complexome profiling dissects the structural organization of the human respiratory supercomplexes in SCAFI(KO) cells. Biochim Biophys Acta Bioenerg 1862, 148414. 10.1016/j.bbabio.2021.148414. 4.Palenikova, P., Harbour, M.E., Prodi, F., Minczuk, M., Zeviani, M., Ghelli, A., and Fernandez-Vizarra, E. (2021). Duplexing complexome profiling with SILAC to study human respiratory chain assembly defects. Biochim Biophys Acta Bioenerg 1862, 148395. 10.1016/j.bbabio.2021.148395. 5.Protasoni, M., Perez-Perez, R., Lobo-Jarne, T., Harbour, M.E., Ding, S., Penas, A., Diaz, F., Moraes, C.T., Fearnley, I.M., Zeviani, M., Ugalde, C., and Fernandez-Vizarra, E. (2020). Respiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV. The EMBO journal 39, e102817. 10.15252/embj.2019102817. Invited
ID: 403 Invited Speakers Pluripotent stem cells and brain organoids for drug discovery of mitochondrial diseases Heinrich Heine University, Düsseldorf, Germany Oral presentation
ID: 347 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity High-throughput single cell analysis reveals progressive mitochondrial DNA mosaicism developing throughout life 1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 3Biosciences Institute, Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK Bibliography
Burr, S. P., et al. (2023). "Cell lineage-specific mitochondrial resilience during mammalian organogenesis." Cell. Alzaydi, M. M., et al. (2023). "Intracellular Chloride Channels Regulate Endothelial Metabolic Reprogramming in Pulmonary Arterial Hypertension." Am J Respir Cell Mol Biol 68(1): 103-115. Kayhanian, S., et al. (2022). "Cell-Free Mitochondrial DNA in Acute Brain Injury." Neurotrauma Rep 3(1): 415-420. Oral presentation
ID: 238 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A coordinated multiorgan metabolic response contributes to human mitochondrial myopathy. 1Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY; 2Weill Cornell Medicine, Department of Pharmacology, New York, NY; 3Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy; 4IRCCS, Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy Oral presentation
ID: 520 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Succinylation as a novel pathogenic mechanism in a children's mitochondrial brain disease 1STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; 2Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA; 3Buck Institute for Research on Aging, Novato, CA 94945, USA; 4Gladstone Institutes and University of California, San Francisco, CA 94158, USA; 5Department of Physics, University of Helsinki, Finland; 6HiLIFE Institute of Biotechnology, University of Helsinki, Finland; 7Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark; 8Unit of Cellular Biology and Mitochondrial Diseases, “Bambino Gesù” Children's Hospital, IRCCS, Rome, Italy; 9Program in Genetics and Genome Biology, The Hospital for Sick Children, Institute of Medical Science University of Toronto, Toronto, Ontario, Canada; 10Division of Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA Bibliography
Gut, P., Matilainen, S., Meyer, J. G., Pällijeff, P., Richard, J., Carroll, C. J., ... & Verdin, E. (2020). SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease. Nature communications, 11(1), 5927. Flash Talk
ID: 226 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The levels and activation state of the pyruvate dehydrogenase complex modulate the SCAFI-dependent organization of the mitochondrial respiratory chain 1Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain; 2Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid, Spain Bibliography
Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C. Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. 2022 Nov 1;34(11):1792-1808.e6. doi: 10.1016/j.cmet.2022.09.005. PMID: 36198313. Flash Talk
ID: 301 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Oxphos deficiency indicates novel functions for the mitochondrial protein import subunit tim50 1Department of Biochemistry and Pharmacology and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia; 2Queensland Children’s Hospital, Department of Metabolic Medicine, South Brisbane, Brisbane, Queensland, 4001, Australia; 3Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia; 4Department of Paediatrics, University of Melbourne, Melbourne, Victoria, 3052, Australia; 5Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia Flash Talk
ID: 300 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Microproteins in metabolic regulation 1Duke-NUS Medical School, Singapore; 2University of Melbourne, Australia; 3University of Utah, USA; 4University of Southampton, UK Bibliography
Lena Ho, PhD (lead PI), is regarded as a pioneer in the field of microprotein research with over 30 primary research articles (5991 citations, H-index of 21) in top-tier journals. With more than 12 years of experience in microprotein discovery, functionalization and therapeutic development, Lena and her team have developed a framework of bioinformatic tools for mining ribo-seq data for disease-relevant small ORF peptides, as well as an extensive range of biochemical tools to validate their function and uncover their molecular mechanism. Lena is an EMBO Young Investigator and HHMI international scholar. Recent publications : 1) Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity. Lee CQE, Kerouanton B, Chothani S, Zhang S, Chen Y, Mantri CK, Hock DH, Lim R, Nadkarni R, Huynh VT, Lim D, Chew WL, Zhong FL, Stroud DA, Schafer S, Tergaonkar V, St John AL, Rackham OJL, Ho L. Nat Commun. 2021 Apr 9;12(1):2130. doi: 10.1038/s41467-021-22397-5. 2) Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis. Liang C, Zhang S, Robinson D, Ploeg MV, Wilson R, Nah J, Taylor D, Beh S, Lim R, Sun L, Muoio DM, Stroud DA, Ho L. Cell Rep. 2022 Aug 16;40(7):111204. doi: 10.1016/j.celrep.2022.111204. 3) Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly. Zhang S, Reljić B, Liang C, Kerouanton B, Francisco JC, Peh JH, Mary C, Jagannathan NS, Olexiouk V, Tang C, Fidelito G, Nama S, Cheng RK, Wee CL, Wang LC, Duek Roggli P, Sampath P, Lane L, Petretto E, Sobota RM, Jesuthasan S, Tucker-Kellogg L, Reversade B, Menschaert G, Sun L, Stroud DA, Ho L. 4) Viral proteases activate the CARD8 inflammasome in the human cardiovascular system. Nadkarni R, Chu WC, Lee CQE, Mohamud Y, Yap L, Toh GA, Beh S, Lim R, Fan YM, Zhang YL, Robinson K, Tryggvason K, Luo H, Zhong F, Ho L. J Exp Med. 2022 Oct 3;219(10):e20212117. doi: 10.1084/jem.20212117. Epub 2022 Sep 21. |
| 3:30pm - 3:50pm | Industry Workshop: Abliva AB Location: Bologna Congress Center - Sala Europa |
| 3:30pm - 4:30pm | Tea Break and poster session Location: Bologna Congress Center Session topics: - Clinical 1: from new genes to old and novel phenotypes - New technological developments and OMICS - Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity |
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ID: 495
Clinical 1: from new genes to old and novel phenotypes Recessive MECR pathogenic variants cause a LHON-like optic neuropathy 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; 3Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy; 4Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy ID: 213
Clinical 1: from new genes to old and novel phenotypes Variants in ATP5F1B are associated with dominantly inherited dystonia 1Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy; 2Northwestern University, Feinberg School of Medicine, Chicago, USA; 3Helmholtz Zentrum München, Technical University of Munich, Munich, Germany; 4Università di Milano, Milan, Italy ID: 143
Clinical 1: from new genes to old and novel phenotypes Toward clinical implementation of quantitative proteomics in the detection of mitochondrial disorders 1University of Melbourne, Parkville, Australia; 2Victoria University, Footscray, Australia; 3Murdoch Children’s Research Institute, Melbourne, Australia; 4Victorian Clinical Genetics Services, Melbourne, Australia; 5National Metabolic Service Auckland City Hospital, Auckland, New Zealand; 6Starship Children's Hospital, Auckland, New Zealand; 7University of Colorado, Aurora, United States of America; 8Centre for Population Genomics, Melbourne, Australia; 9Garvan Institute of Medical Research, Sydney, Australia Bibliography
Amarasekera S.S.C., Hock D.H., Lake N.J., Calvo S.E., Grønborg S.W., Krzesinski E.I., Amor D.J., Fahey M.C., Simons C., Wibrand F., Mootha V.K., Lek M., Lunke S., Stark Z., Østergaard E., Christodoulou J., Thorburn D.R., *Stroud D.A., *Compton A.G. (2023) Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease. In revision. van Bergen N.J., Gunanayagam K., Bournazos A.M., Walvekar A.S., Warmoes M.O., Semcesen L.N., Lunke S., Bommireddipalli S., Sikora T., Jones D.L., Garza D., Sebire D., Gooley S., McLean C.A., Naidoo P., Rajasekaran M., *Stroud D.A., *Linster C.L., *Wallis M., *Cooper S.T., *Christodoulou J. (2023) Severe NAD(P)HX dehydratase (NAXD) neurometabolic syn-drome may present in adulthood after mild head trauma. IJMS 24,4. 10.3390/ijms24043582. Robinson D.R.L., Hock D.H., Muellner-Wong L., Kugapreethan R., Reljic B., Surgenor E.S., Rodrigues C.H.M., Caruana N.J., *Stroud D.A. (2022) Applying Sodium Carbonate Extraction Mass Spectrometry to Investigate Defects in the Mitochondrial Respiratory Chain. Front. Cell Dev. Biol. 10, 786268. Hock D.H., Robinson D.R.L., *Stroud D.A. (2020) Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome. Biochem. J. 477, 4085. Helman G., Compton A.G., Hock D.H., Walkiewicz M., Brett G.R., Pais L., Tan T.Y., De Paoli-Iseppi R., Clark M.B., Christodoulou J., White S.M., Thorburn D.R., Stroud D.A., Stark Z., Simons C. (2021) Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10. Hum. Mutat. 42, 29. Frazier A.E., Compton A.G., Kishita Y., Hock D.H., Welch A.E., Amarasekera S.S.C., Rius R., Formosa L.E., Imai-Okazaki A., Francis D., Wang M., Lake N.J., Tregoning S., Jabbari J.S., Lucattini A., Nitta K.R., Ohtake A., Murayama K., Amor D.J., McGillivray G., Wong F.Y., van der Knaap M.S., Jeroen Vermeulen R., Wiltshire E.J., Fletcher J.M., Lewis B., Baynam G., Ellaway C., Balasubramaniam S., Bhattacharya K., Freckmann M.L., Arbuckle S., Rodriguez M., Taft R.J., Sadedin S., Cowley M.J., Minoche A.E., Calvo S.E., Mootha V.K., Ryan M.T., Okazaki Y., Stroud D.A., Simons C., Christodoulou J., Thorburn D.R. (2021) Fatal perinatal mitochondrial cardiac failure caused by recurrent de novo duplications in the ATAD3 locus. Med 2, 49. Hock D.H., Reljic B., Ang C.S., Muellner-Wong L., Mountford H.S., Compton A.G., Ryan M.T., Thorburn D.R., *Stroud D.A. (2020) HIGD2A Is Required for Assembly of the COX3 Module of Human Mitochondrial Complex IV. Mol. Cell Proteomics. 19, 107541. *, corresponding author ID: 611
Clinical 1: from new genes to old and novel phenotypes A DNM2-related myopathy mimicking a primary mitochondrial disorder 1Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.; 2Department of Neurosciences, Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; 3Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. ID: 594
Clinical 1: from new genes to old and novel phenotypes Assessing the association of mitochondrial DNA genes with Primary Mitochondrial Disease using the ClinGen Clinical Validity Framework 1Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA; 2Illumina Laboratory Services, Illumina Inc., San Diego, CA; 3Center for Personalized Medicine, Department of Pathology & Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA; 4Keck School of Medicine, University of Southern California, Los Angeles, CA; 5Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 6Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom ID: 282
Clinical 1: from new genes to old and novel phenotypes Functional characterisation of the m.8424T>C MT-ATP8 variant using quantitative proteomics 1University of Melbourne, Parkville, Australia; 2Victoria University, Footscray, Australia; 3Murdoch Children’s Research Institute, Melbourne, Australia; 4Victorian Clinical Genetics Services, Melbourne, Australia; 5Australian Genomics, Melbourne, Australia ID: 493
Clinical 1: from new genes to old and novel phenotypes COX18 variants cause isolated Complex IV deficiency associated with neonatal hypertrophic cardiomyopathy, myopathy and axonal sensory neuropathy 1Dino Ferrari Center, University of Milan, Italy; 2IRCCS Cà Granda Ospedale Maggiore Policlinico Milan, Italy; 3ASST Papa Giovanni XXIII, Bergamo, Italy ID: 255
Clinical 1: from new genes to old and novel phenotypes Severe mitochondrial encephalomyopathy caused by de novo variants in OPA1 1Muscular and Neurodegenerative Disorders Unit, Children Hospital Bambino Gesù; 2Cellular biology and mitochondrial diseases diagnostics, Children Hospital Bambino Gesù; 3Department of Chemistry Life Sciences and Environmental Sustainability, University of Parma; 4Metabolism Division, Children Hospital Bambino Gesù, Rome; 5Molecular Medicine, IRCCS Stella Maris, Pisa Bibliography
1) Hypoventilation and sleep hypercapnia in a case of congenital variant-like Rett syndrome. Ghirardo S, Sabatini L, Onofri A, Testa MBC, Paglietti MG, Diodato D, Travaglini L, Stregapede F, Ciofi Degli Atti ML, Cherchi C, Cutrera R. Ital J Pediatr. 2022 Sep 7;48(1):167. doi: 10.1186/s13052-022-01359-7. PMID: 36071486 Free PMC article. 2) Neuropsychological and behavioral profile in a cohort of Becker muscular dystrophy pediatric patients. Cumbo F, Tosi M, Catteruccia M, Diodato D, Nicita F, Capitello TG, Alfieri P, Vicari S, Bertini E, D'Amico A. Neuromuscul Disord. 2022 Sep;32(9):736-742. doi: 10.1016/j.nmd.2022.07.402. Epub 2022 Jul 27. PMID: 35953344 4) Response to: Phenotypic heterogeneity of Leigh syndrome due to NDUFA12 variants is multicausal. Torraco A, Maroofian R, Rötig A, Bertini E, Ghezzi D, Carrozzo R, Diodato D. Hum Mutat. 2022 Jan;43(1):99-100. doi: 10.1002/humu.24303. Epub 2021 Dec 9. PMID: 34888984 No abstract available. 5) Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases. Ardissone A, Bruno C, Diodato D, Donati A, Ghezzi D, Lamantea E, Lamperti C, Mancuso M, Martinelli D, Primiano G, Procopio E, Rubegni A, Santorelli F, Schiaffino MC, Servidei S, Tubili F, Bertini E, Moroni I. Orphanet J Rare Dis. 2021 Oct 9;16(1):413. doi: 10.1186/s13023-021-02029-3. PMID: 34627336 Free PMC article. 6) Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. Zheng WQ, Pedersen SV, Thompson K, Bellacchio E, French CE, Munro B, Pearson TS, Vogt J, Diodato D, Diemer T, Ernst A, Horvath R, Chitre M, Ek J, Wibrand F, Grange DK, Raymond L, Zhou XL, Taylor RW, Ostergaard E. Hum Mol Genet. 2022 Feb 21;31(4):523-534. doi: 10.1093/hmg/ddab257. PMID: 34508595 7) Age-related sensory neuropathy in patients with spinal muscular atrophy type 1. Pro S, Tozzi AE, D'Amico A, Catteruccia M, Cherchi C, De Luca M, Nicita F, Diodato D, Cutrera R, Bertini E, Valeriani M. Muscle Nerve. 2021 Nov;64(5):599-603. doi: 10.1002/mus.27389. Epub 2021 Aug 23. PMID: 34368972 8) Antenatal Membranous Nephropathy and Type 2 (Axonal) Charcot-Marie-Tooth With Mutations in the Metallo-Membrane Endopeptidase Gene: A Call for Family Screening and Pharmacovigilance. Nortier JL, Remiche G, Delrée P, Nauta J, Notermans NC, Vivarelli M, Diodato D, Solé G, Debiec H, Ronco P. Kidney Int Rep. 2021 May 12;6(7):1981-1986. doi: 10.1016/j.ekir.2021.04.034. eCollection 2021 Jul. PMID: 34307994 Free PMC article. No abstract available. 9) Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases. Ticci C, Orsucci D, Ardissone A, Bello L, Bertini E, Bonato I, Bruno C, Carelli V, Diodato D, Doccini S, Donati MA, Dosi C, Filosto M, Fiorillo C, La Morgia C, Lamperti C, Marchet S, Martinelli D, Minetti C, Moggio M, Mongini TE, Montano V, Moroni I, Musumeci O, Pancheri E, Pegoraro E, Primiano G, Procopio E, Rubegni A, Scalise R, Sciacco M, Servidei S, Siciliano G, Simoncini C, Tolomeo D, Tonin P, Toscano A, Tubili F, Mancuso M, Battini R, Santorelli FM. J Clin Med. 2021 May 12;10(10):2063. doi: 10.3390/jcm10102063. PMID: 34065803 Free PMC article. 10) Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation. Torraco A, Nasca A, Verrigni D, Pennisi A, Zaki MS, Olivieri G, Assouline Z, Martinelli D, Maroofian R, Rizza T, Di Nottia M, Invernizzi F, Lamantea E, Longo D, Houlden H, Prokisch H, Rötig A, Dionisi-Vici C, Bertini E, Ghezzi D, Carrozzo R, Diodato D. Hum Mutat. 2021 Jun;42(6):699-710. doi: 10.1002/humu.24195. Epub 2021 Mar 25. PMID: 33715266 ID: 438
Clinical 1: from new genes to old and novel phenotypes Bi-allelic TEFM variants are associated with a treatable mitochondrial myopathy 1Unit of Cellular Biology and Diagnosis of Mitochondrial Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome Italy.; 2Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.; 3Dipartimento Di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy. Bibliography
1-Torraco A, Morlino S, Rizza T, Di Nottia M, Bottaro G, Bisceglia L, Montanari A, Cappa M, Castori M, Bertini E, Carrozzo R. A novel homozygous variant in COX5A causes an attenuated phenotype with failure to thrive, lactic acidosis, hypoglycemia, and short stature. Clin Genet. 2022 Jul;102(1):56-60. 2-Torraco A, Nasca A, Verrigni D, Pennisi A, Zaki MS, Olivieri G, Assouline Z, Martinelli D, Maroofian R, Rizza T, Di Nottia M, Invernizzi F, Lamantea E, Longo D, Houlden H, Prokisch H, Rötig A, Dionisi-Vici C, Bertini E, Ghezzi D, Carrozzo R, Diodato D. Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation. Hum Mutat. 2021 Jun;42(6):699-710. 3-Torraco A, Stehling O, Stümpfig C, Rösser R, De Rasmo D, Fiermonte G, Verrigni D, Rizza T, Vozza A, Di Nottia M, Diodato D, Martinelli D, Piemonte F, Dionisi-Vici C, Bertini E, Lill R, Carrozzo R. ISCA1 mutation in a patient with infantile-onset leukodystrophy causes defects in mitochondrial [4Fe-4S] proteins. Hum Mol Genet. 2018 Oct 15;27(20):3650. ID: 486
Clinical 1: from new genes to old and novel phenotypes TOMM40L as a new causative gene for autosomal recessive mitochondrial disease. 1Laboratorio de Enfermedades Mitocondriales. Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain.; 2Unidad Pediátrica de Enfermedades Raras, Enfermedades Mitocondriales y Metabólicas Hereditarias, Hospital 12 de Octubre, E-28041, Madrid, Spain.; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain. Bibliography
Rodríguez-García, M. E., Cotrina-Vinagre, F. J., et al., (2022). First splicing variant in HECW2 with an autosomal recessive pattern of inheritance and associated with NDHSAL. Human mutation, 43(10), 1361–1367. https://doi.org/10.1002/humu.24426 Lopes Abath Neto, O., Medne, L., Donkervoort, S., Rodríguez-García, M. E., Bolduc, V., Hu, Y., Guadagnin, E., Foley, A. R., Brandsema, J. F., Glanzman, A. M., Tennekoon, G. I., Santi, M., Berger, J. H., Megeney, L. A., Komaki, H., Inoue, M., Cotrina-Vinagre, F. J.,et al., (2021). MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase. Brain : a journal of neurology, 144(9), 2722–2731. https://doi.org/10.1093/brain/awab275 Cotrina-Vinagre, F. J., et al., (2021). Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants. Molecular genetics and metabolism, 133(2), 201–210. https://doi.org/10.1016/j.ymgme.2021.02.007 Rodríguez-García, M. E., Cotrina-Vinagre, F. J., et al., (2021). New subtype of PCH1C caused by novel EXOSC8 variants in a 16-year-old Spanish patient. Neuromuscular disorders : NMD, 31(8), 773–782. https://doi.org/10.1016/j.nmd.2021.05.008 Rodríguez-García, M. E., Cotrina-Vinagre, F. J., et al., (2019). A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome. European journal of human genetics : EJHG, 27(9), 1369–1378. https://doi.org/10.1038/s41431-019-0418-1 ID: 528
Clinical 1: from new genes to old and novel phenotypes A primary cardiological phenotype caused by an inherited mtDNA single deletion: a case report from an Italian pedigree 1Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy; 2Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; 3Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany; 4Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy Bibliography
1) Mancuso M, Orsucci D, Angelini C, Bertini E, Carelli V, Comi GP, Donati MA, Federico A, Minetti C, Moggio M, Mongini T, Santorelli FM, Servidei S, Tonin P, Toscano A, Bruno C, Bello L, Caldarazzo Ienco E, Cardaioli E, Catteruccia M, Da Pozzo P, Filosto M, Lamperti C, Moroni I, Musumeci O, Pegoraro E, Ronchi D, Sauchelli D, Scarpelli M, Sciacco M, Valentino ML, Vercelli L, Zeviani M, Siciliano G. Redefining phenotypes associated with mitochondrial DNA single deletion. J Neurol. 20 2) Grady JP, Campbell G, Ratnaike T, Blakely EL, Falkous G, Nesbitt V, Schaefer AM, McNally RJ, Gorman GS, Taylor RW, Turnbull DM, McFarland R (2014) Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain 137:323–334 3) Yamashita S, Nishino I, Nonaka I, Goto Y (2008) Genotype and phenotype analyses in 136 patients with single large-scale mitochondrial DNA deletions. J Hum Genet 53:598–606 15 May;262(5):1301-9. doi: 10.1007/s00415-015-7710-y. Epub 2015 Mar 26. Erratum in: J Neurol. 2015 Dec;262(12):2800. PMID: 25808502. 4) Chinnery PF, DiMauro S, Shanske S, Schon EA, Zeviani M, Mariotti C, Carrara F, Lombes A, Laforet P, Ogier H, Jaksch M, Lochmüller H, Horvath R, Deschauer M, Thorburn DR, Bindoff LA, Poulton J, Taylor RW, Matthews JN, Turnbull DM. Risk of developing a mitochondrial DNA deletion disorder. Lancet. 2004 Aug 14-20;364(9434):592-6. doi: 10.1016/S0140-6736(04)16851-7. PMID: 15313359. ID: 150
Clinical 1: from new genes to old and novel phenotypes Genetic characterization of a large cohort of Spanish patients with TK2 deficiency. A founder effect of two TK2 variants partially contributes to a higher prevalence of the disorder in Spain. 1Hospital Universitario 12 de Octubre, imas12 Research Institute, Madrid, Spain; 2Spanish Network for Biomedical Research in Rare Diseases (CIBERER); 3Fundación Galega de Medicina Xenómica, Santiago de Compostela, Spain; 4Instituto de Investigación Sanitaria, Hospital Universitario FundaciónJiménez Díaz, Madrid, Spain; 5Research Group on Neuromuscular and Mitochondrial Diseases, Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona; 6Hospital Universitari I Politècnic La Fe, Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe, Valencia; 7Sant Joan de Déu Research Institute, Sant Joan de Déu Hospital, Barcelona, Spain.; 8Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío, Sevilla, Spain.; 9Center for Biomedical Network Research on Neurodegenerative Disorders (CIBERNED) Bibliography
1.Domínguez-González C, Fernández-Torrón R, Moore U, de Fuenmayor-Fernández de la Hoz CP, Vélez-Gómez B, Cabezas JA, Alonso-Pérez J, González-Mera L, Olivé M, García-García J, Moris G, León Hernández JC, Muelas N, Servian-Morilla E, Martin MA, Díaz-Manera J, Paradas C. Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis. J Neurol. 2022 Jul;269(7):3550-3562. doi: 10.1007/s00415-021-10957-0. Epub 2022 Mar 14. PMID: 35286480; PMCID: PMC9217784. 2.Berardo A, Domínguez-González C, Engelstad K, Hirano M. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-235. doi: 10.3233/JND-210786. PMID: 35094997; PMCID: PMC9028656. 3.Domínguez-González C, Madruga-Garrido M, Hirano M, Martí I, Martín MA, Munell F, Nascimento A, Olivé M, Quan J, Sardina MD, Martí R, Paradas C. Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency. Orphanet J Rare Dis. 2021 Oct 2;16(1):407. doi: 10.1186/s13023-021-02030-w. PMID: 34600563; PMCID: PMC8487573. 4.Domínguez-González C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodríguez FJ, Donati MA, Kleinsteuber K, Martí I, Martín-Hernández E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Álvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Martí R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019 Aug;86(2):293-303. doi: 10.1002/ana.25506. Epub 2019 Jun 17. PMID: 31125140; PMCID: PMC7586249. 5.Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, Fuiza-Luces C, García García J, Morís G, Olivé M, Miralles F, Díaz-Manera J, Caballero C, Méndez-Ferrer B, Martí R, García Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MÁ, Paradas C. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019 May 6;14(1):100. doi: 10.1186/s13023-019-1071-z. PMID: 31060578; PMCID: PMC6501326. 6.Domínguez-González C, Hernández-Voth A, de Fuenmayor-Fernández de la Hoz CP, Guerrero LB, Morís G, García-García J, Muelas N, León Hernández JC, Rabasa M, Lora D, Blázquez A, Arenas J, Martin MÁ. Metrics of progression and prognosis in untreated adults with thymidine kinase 2 deficiency: An observational study. Neuromuscul Disord. 2022 Sep;32(9):728-735. doi: 10.1016/j.nmd.2022.07.399. Epub 2022 Jul 16. PMID: 35907766. ID: 198
Clinical 1: from new genes to old and novel phenotypes HSD17B10 interacts with CBR4 to form human mitochondrial 3-ketoacyl-acyl carrier protein reductase 2 (KAR2) in the mitochondrial fatty acid synthesis pathway Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland Bibliography
I.Shvetsova, A., Masud, A. J., Schneider, L., Bergmann, U., Monteuuis, G., Miinalainen, I. J., ... & Kastaniotis, A. J. (2021). A hunt for OM45 synthetic petite interactions in Saccharomyces cerevisiae reveals a role for Miro GTPase Gem1p in cristae structure maintenance. MicrobiologyOpen, 10(5), e1238. doi.org/10.1002/mbo3.1238 II.Masud, A. J., Kastaniotis, A. J., Rahman, M. T., Autio, K. J., & Hiltunen, J. K. (2019). Mitochondrial acyl carrier protein (ACP) at the interface of metabolic state sensing and mitochondrial function. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 118540. doi.org/10.1016/j.bbamcr.2019.118540 III.Monteuuis, G., Suomi, F., Kerätär, J. M., Masud, A. J. & Kastaniotis, A. J. (2017). A conserved mammalian mitochondrial isoform of acetyl-CoA carboxylase ACC1 provides the malonyl-CoA essential for mitochondrial biogenesis in tandem with ACSF3. Biochemical Journal, 474(22), 3783-3797. doi.org/10.1042/BCJ20170416 IV.Nair, R. R., Kerätär, J. M., Autio, K. J., Masud, A. J., Finnilä, M. A., Autio-Harmainen, H. I., Miinalainen, I. J., Nieminen, P. A., Hiltunen, J. K. & Kastaniotis, A. J. (2017). Genetic modifications of Mecr reveal a role for mitochondrial 2-enoyl-CoA/ACP reductase in placental development in mice. Human Molecular Genetics, 26(11), 2104-2117. doi.org/10.1093/hmg/ddx105 V.Masud, A. J. M., Mia, M. A., Islam, M. M., Begum, S. N., & Prodhan, S. H. (2014). Morpho-Molecular Screening of Rice (Oryza Sativa L.) Genotypes At Seedling Stage for Salt Tolerance. The Journal of Microbiology, Biotechnology and Food Sciences, 4(2), 164. doi.org/10.15414/jmbfs.2014.4.2.164-169 ID: 668
Clinical 1: from new genes to old and novel phenotypes Novel atypical variants causing pyruvate dehydrogenase complex deficiency 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2Centre of inherited metabolic diseases, Karolinska University Hospital, Stockholm, Sweden; 3Neuropediatric Unit, Dept of Women’s, and Children's Health, Karolinska Institutet, Stockholm, Sweden; 4Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ID: 492
Clinical 1: from new genes to old and novel phenotypes Novel genetic discoveries detected using diagnostic OMICSs in patients suspected to suffer from multiple acyl-CoA dehydrogenation deficiency 1Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands; 2Institute of Neurogenomics, Helmholtz Zentrum München, Germany; 3Institute of Human Genetics, School of Medicine, Technical University Munich, München, Germany.; 4Department of Pediatrics, Graduate School of Medicine, Gifu University Hospital, Gifu, Japan.; 5Department of Informatics, Technical University of Munich, Garching, Germany.; 6Department of Biochemical Genetics, St James's University Hospital, Leeds, UK.; 7Department of Pediatrics, Sheffield Children's Hospital, Sheffield, UK.; 8Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel.; 9Department of Inborn Errors of Metabolism and Paediatrics, The Institute of Mother and Child, Warsaw, Poland.; 10Department of Pediatrics, Hannover Medical School, Hannover, Germany.; 11Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.; 12Center for Inherited Metabolic Disorders, Guy’s & St Thomas’ Hospital NHS Foundation Trust, London, UK.; 13University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.; 14Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; 15Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA; 16Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.; 17UofL Physicians Novak Center for Children's Health, Louisville, USA.; 18Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, UK; 19Sheffield Teaching Hospitals NHS Trust, University of Sheffield, Sheffield, UK; 20Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; 21Clinical Genetics Center, Gifu University Hospital, Gifu, Japan.; 22Department of Clinical Chemistry, Sheffield Children’s Hospital, Sheffield, UK. Bibliography
First and shared first (3): Mosegaard S*, Dipace G*, Bross P, Carlsen J, Gregersen N, Olsen RKJ. 2020. ”Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism”. International Journal of Molecular Sciences;21(11):3847. doi: 10.3390/ijms21113847. Mosegaard S*, Bruun GH*, Flyvbjerg KF, Bliksrud YT, Gregersen N, Dembic M, Annexstad E, Tangeraas T, Olsen RKJ, Andresen BS. 2017. “An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency”. Molecular Genetics and Metabolism;122(4):182-188. doi: 10.1016/j.ymgme.2017.10.014. Olsen RKJ*, Koňaříková E*, Giancaspero TA*, Mosegaard S*, Boczonadi V*, Mataković L*, ….. Barile M, Prokisch H. 2016. ”Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency”. American Journal of Human Genetics;98(6):1130-1145. doi: 10.1016/j.ajhg.2016.04.006. Co-author (5): V.A. Yépez, M. Gusic, R. Kopajtich, C. Mertes, N.H. Smith, C.L. Alston, R. Ban, S. Beblo, R. Berutti, H. Blessing, E. Ciara, F. Distelmaier, P. Freisinger, J. Häberle, S.J. Hayflick, M. Hempel, Y.S. Itkis, Y. Kishita, T. Klopstock, T.D. Krylova, C. Lamperti, D. Lenz, C. Makowski, S. Mosegaard, M.F. Müller, G. Muñoz-Pujol, A. Nadel, A. Ohtake, Y. Okazaki, E. Procopio, T. Schwarzmayr, J. Smet, C. Staufner, S.L. Stenton, T.M. Strom, C. Terrile, F. Tort, R. Van Coster, A. Vanlander, M. Wagner, M. Xu, F. Fang, D. Ghezzi, J.A. Mayr, D. Piekutowska-Abramczuk, A. Ribes, A. Rötig, R.W. Taylor, S.B. Wortmann, K. Murayama, T. Meitinger, J. Gagneur, H. Prokisch, Clinical implementation of RNA sequencing for Mendelian disease diagnostics, Genome Med. 14 (2022) 38. https://doi.org/10.1186/s13073-022-01019-9. Fogh S, Dipace G, Bie A, Veiga-da-Cunha M, Hansen J, Kjeldsen M, Mosegaard S, Ribes A, Gregersen N, Aagaard L, Van Schaftingen E, Olsen RKJ. “Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?” J Inherit Metab Dis. 2021 Sep;44(5):1215-1225. doi: 10.1002/jimd.12394. Muru K., Reinson K., Künnapas K., Lilleväli H., Nochi Z., Mosegaard S., Pajusalu S., Olsen R. and Õunap K. “FLAD1 Asso-ciated Multiple Acyl-CoA Dehydrogenase Deficiency Identified by Newborn Screening.”. Molecular Genetics & Genomic Medicine;7(9). doi: 10.1002/mgg3.915. García-Villoria J., de Azua B., Tort F., Mosegaard S., Matalonga L., Ugarteburu O., Teixidó L., Olsen R. and Ribes A. “FLAD1, a recently described gene associated to multiple acyl-CoA dehydrogenase deficiency (MADD) is mutated in a patient with myopathy, scoliosis and cataracts.”. Clinical Genetics;94(6):592-593. doi: 10.1111/cge.13452. Auranen M., Paetau A., Piirilä P., Pohju A., Salmi T., Lamminen A., Thure H., Löfberg M., Mosegaard S., Olsen R., Tyni T. “FLAD1 gene mutation causes riboflavin responsive MADD disease”. Neuromuscular Disorders;27(6):581-584. doi: 10.1016/j.nmd.2017.03.003. ID: 439
Clinical 1: from new genes to old and novel phenotypes The Australian genomics mitochondrial flagship: a national program delivering mitochondrial diagnoses 1Murdoch Children's Research Institute, Melbourne, Australia; 2University of Melbourne, Melbourne, Australia; 3Victorian Clinical Genetics Services, Melbourne,; 4Sydney Children’s Hospitals Network, Westmead, Australia; 5Macquarie University, Sydney, Australia; 6Women’s and Children’s Hospital, Adelaide, Australia; 7Tasmanian Clinical Genetics Service, Hobart, Australia; 8Queensland Children’s Hospital, Brisbane, Australia; 9Wesley Hospital, Brisbane, Australia; 10Garvan Institute, Sydney, Australia; 11Royal Melbourne Hospital, Melbourne, Australia; 12Royal Adelaide Hospital, Adelaide, Australia; 13John Hunter Hospital, Newcastle, Australia; 14Harry Perkins Institute of Medical Research, Perth, Australia; 15Perth Children’s Hospital, Perth, Australia; 16Yale School of Medicine, New Haven, CT, USA; 17Royal Perth Hospital, Perth, Australia; 18Royal Children’s Hospital, Melbourne, Australia; 19Mito Foundation, Sydney, Australia; 20Mater Hospital, Brisbane, Australia; 21Genetic Health Queensland, Brisbane, Australia; 22Monash University, Melbourne, Australia; 23Westmead Hospital, Westmead, Australia; 24Royal Hobart Hospital, Hobart, Australia Bibliography
Granata C, Caruana NJ, Botella J, Jamnick NA, Huynh K, Kuang J, Janssen HA, Reljic B, Mellett NA, Laskowski A, Stait TL, Frazier AE, Coughlan MT, Meikle PJ, Thorburn DR, Stroud DA and Bishop DJ (2021) Training-induced bioenergetic improvement in human skeletal muscle is associated with non-stoichiometric changes in the mitochondrial proteome without reorganisation of respiratory chain content. Nat Commun 12:7056 Wu Y, Balasubramaniam S, Rius R, Thorburn DR, Christodoulou J & Goranitis I (2021) Genomic sequencing for the diagnosis of childhood mitochondrial disorders: a health economic evaluation. Eur J Hum Genet 30:577-586 Frazier AE, Compton AG, Kishita Y, Hock DH, Welch AME, Amarasekera SS, Rius R, Formosa LE, Imai-Okazaki A, Francis D, Wang N, Lake NJ, Tregoning S, Jabbari JS, Lucattini A, Nitta KR, Ohtake A, Murayama K, Amor DJ, McGillivray G, Wong FY, van der Knaap MS, Vermeulen RJ, Wiltshire EJ, Fletcher JM, Lewis B, Baynam G, Ellaway C, Balasubramaniam S, Bhattacharya K, Freckmann ML, Arbuckle S, Rodriguez M, Taft RJ, Sadedin S, Cowley MJ, Minoche AE, Calvo SE, Mootha VK, Ryan MT, Okazaki V, Stroud DA, Simons C, Christodoulou J and Thorburn DR (2021) Fatal Perinatal Mitochondrial Cardiac Failure Caused by Recurrent De Novo Duplications in the ATAD3 Locus. Med 2:49-73 Riley LG, Cowley MJ, Gayevskiy V, Minoche AE, Puttick C, Thorburn DR, Rius, Compton AG, Menezes MJ, Battacharya K, Coman D, Ellaway C, Alexander IE, Adams L, Kava M, Robinson J, Sue CM, Balasubramaniam S and Christodoulou J (2020) The diagnostic utility of genome sequencing in a pediatric cohort with suspected mitochondrial disease. Genet Med 22:1254-1261 ID: 649
Clinical 1: from new genes to old and novel phenotypes A new family with a case of severe early-onset muscle fatigue and a peculiar maternally inherited painful swelling in chewing muscles associated with homoplasmic m.15992A>T mutation in mitochondrial tRNAPro 1Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy; 3Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Bibliography
1. Auré K, Fayet G, Chicherin I, Rucheton B, Filaut S, Heckel AM, Eichler J, Caillon F, Péréon Y, Entelis N, Tarassov I, Lombès A. Homoplasmic mitochondrial tRNAPro mutation causing exercise-induced muscle swelling and fatigue. Neurol Genet. 2020 Jul 15;6(4):e480. ID: 358
Clinical 1: from new genes to old and novel phenotypes A novel MT-ATP6 variant associated with complicated ataxia in two unrelated Italian patients: case report and functional studies. 1Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta; 2Department of Pathophysiology and Transplantation (DEPT), University of Milan ID: 618
Clinical 1: from new genes to old and novel phenotypes Biallelic pathogenic variants of PARS2 cause Developmental and Epileptic Encephalopathy with Spike-and-Wave Activation in Sleep 1IRCCS, Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy; 3Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Italy. ID: 548
Clinical 1: from new genes to old and novel phenotypes Novel KARS1 mutation causes early-onset lethal cardiomyopathy 1IRCCS Istituto Giannina Gaslini, Genoa; 2IRCCS Fondazione Stella Maris, Calambrone (PI); 3IRCCS Ospedale Bambin Gesù, Rome ID: 277
Clinical 1: from new genes to old and novel phenotypes The ER-MITO (Emilia Romagna-Mitochondrial) project: prevalence and genetics of Chronic Progressive External Ophthalmoplegia (CPEO) in an Italian region 1IRCCS Institute of Neurological Sciences of Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy Bibliography
Primary mitochondrial myopathy: 12-month follow-up results of an Italian cohort. J Neurol. 2022; 269(12): 6555–6565. Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Res. 2022 Aug 26; 50(15): 8749–8766 Rapamycin rescues mitochondrial dysfunction in cells carrying the m.8344A > G mutation in the mitochondrial tRNALys. Mol Med. 2022; 28: 90. Published online 2022 Aug 3. doi: 10.1186/s10020-022-00519-z ID: 504
Clinical 1: from new genes to old and novel phenotypes UCHL1 missense and loss-of-function variants as an emerging cause of autosomal dominant optic atrophy (ADOA) 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy; 3Ospedale Oftalmico Roma, Rome, Italy; 4Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy ID: 345
Clinical 1: from new genes to old and novel phenotypes Mitochondrial dysfunction in patients with early-onset UFM1-linked encephalopathy 1National Centre for Mitochondrial Diseases, Nice Teaching Hospital (CHU de Nice), Department of Medical Genetics, Nice, France; 2Université Côte d'Azur, CHU, Inserm, CNRS, IRCAN, France; 3APHM, La Timone Hospital, Department of Neuropediatrics, Marseille, France Bibliography
UQCRC2-related mitochondrial complex III deficiency, about 7 patients. Bansept C, Gaignard P, Lebigot E, Eyer D, Delplancq G, Hoebeke C, Mazodier K, Ledoyen A, Rouzier C, Fragaki K, Ait-El-Mkadem Saadi S, Philippe C, Bruel AL, Faivre L, Feillet F, Abi Warde MT. Mitochondrion. 2022 Dec 9;68:138-144. doi: 10.1016/j.mito.2022.12.001. ABEILLE: a novel method for ABerrant Expression Identification empLoying machine LEarning from RNA-sequencing data. Labory J, Le Bideau G, Pratella D, Yao JE, Ait-El-Mkadem Saadi S, Bannwarth S, El-Hami L, Paquis-Fluckinger V, Bottini S. Bioinformatics. 2022 Oct 14;38(20):4754-4761. doi: 10.1093/bioinformatics/btac603. Splicing variants in NARS2 are associated with milder phenotypes and intra-familial variability. Ait-El-Mkadem Saadi S, Kaphan E, Morales Jaurrieta A, Fragaki K, Chaussenot A, Bannwarth S, Maues De Paula A, Paquis-Flucklinger V, Rouzier C. Eur J Med Genet. 2022 Dec;65(12):104643. doi: 10.1016/j.ejmg.2022.104643. A Survey of Autoencoder Algorithms to Pave the Diagnosis of Rare Diseases. Pratella D, Ait-El-Mkadem Saadi S, Bannwarth S, Paquis-Fluckinger V, Bottini S. Int J Mol Sci. 2021 Oct 8;22(19):10891. doi: 10.3390/ijms221910891. Improved detection of mitochondrial DNA instability in mitochondrial genome maintenance disorders. Bris C, Goudenège D, Desquiret-Dumas V, Gueguen N, Bannwarth S, Gaignard P, Rucheton B, Trimouille A, Allouche S, Rouzier C, Saadi S, Jardel C, Slama A, Barth M, Verny C, Spinazzi M, Cassereau J, Colin E, Armelle M, Pereon Y, Martin-Negrier ML, Paquis-Flucklinger V, Letournel F, Lenaers G, Bonneau D, Reynier P, Amati-Bonneau P, Procaccio V. Genet Med. 2021 Sep;23(9):1769-1778. doi: 10.1038/s41436-021-01206-w. CHCHD10-Related Disorders. Ait-El-Mkadem Saadi S, Chaussenot A, Bannwarth S, Rouzier C, Paquis-Flucklinger V. 2015 Jul 1 [updated 2021 May 27]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. Multi-Omics Approaches to Improve Mitochondrial Disease Diagnosis: Challenges, Advances, and Perspectives. Labory J, Fierville M, Ait-El-Mkadem S, Bannwarth S, Paquis-Flucklinger V, Bottini S. Front Mol Biosci. 2020 Nov 2;7:590842. doi: 10.3389/fmolb.2020.590842. Single-fiber studies for assigning pathogenicity of eight mitochondrial DNA variants associated with mitochondrial diseases. Zereg E, Chaussenot A, Morel G, Bannwarth S, Sacconi S, Soriani MH, Attarian S, Cano A, Pouget J, Bellance R, Tranchant C, Lannes B, de Paula AM, Saadi Ait-El-Mkadem S, Chafino B, Berthet M, Fragaki K, Paquis-Flucklinger V, Rouzier C. Hum Mutat. 2020 Aug;41(8):1394-1406. doi: 10.1002/humu.24037. NDUFS6 related Leigh syndrome: a case report and review of the literature. Rouzier C, Chaussenot A, Fragaki K, Serre V, Ait-El-Mkadem S, Richelme C, Paquis-Flucklinger V, Bannwarth S. J Hum Genet. 2019 Jul;64(7):637-645. doi: 10.1038/s10038-019-0594-4. MT-CYB deletion in an encephalomyopathy with hyperintensity of middle cerebellar peduncles. Chaussenot A, Rouzier C, Fragaki K, Sacconi S, Ait-El-Mkadem S, Paquis-Flucklinger V, Bannwarth S. Neurol Genet. 2018 Sep 19;4(5):e268. doi: 10.1212/NXG.0000000000000268. eCollection 2018 Oct. PMID: 30294674 Targeted next generation sequencing with an extended gene panel does not impact variant detection in mitochondrial diseases. Plutino M, Chaussenot A, Rouzier C, Ait-El-Mkadem S, Fragaki K, Paquis-Flucklinger V, Bannwarth S. BMC Med Genet. 2018 Apr 7;19(1):57. doi: 10.1186/s12881-018-0568-y. PMID: 29625556 ID: 580
Clinical 1: from new genes to old and novel phenotypes A novel dominant variant in the ISCU gene is associated with mitochondrial myopathy 1Maria Sklodowska-Curie, Medical Academy in Warsaw, Poland; 2MedGen Medical Center, Warsaw, Poland; 3Institute of Psychiatry and Neurology, Warsaw, Poland Bibliography
1. Mochel F, Knight MA, Tong WH, Hernandez D, Ayyad K, Taivassalo T, Andersen PM, Singleton A, Rouault TA, Fischbeck KH, Haller RG. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet 2008;82:652–60. 2. Olsson A, Lind L, Thornell LE, Holmberg M. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum Mol Genet 2008;17:1666–72. 3. Legati A., Reyes A., Ceccatelli Berti C., Stehling O., Marchet S., Lamperti C., Ferrari A., Robinson A.J., Mühlenhoff U., Lill R., et al. A Novel de Novo Dominant Mutation in ISCU Associated with Mitochondrial Myopathy. J. Med. Genet. 2017;54:815–824. ID: 499
Clinical 1: from new genes to old and novel phenotypes Expanding the spectrum of clinical presentations associated with COA8 pathogenic 1IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Dino Ferrari Center, University of Milan, Milan, Italy ID: 332
Clinical 1: from new genes to old and novel phenotypes A novel mitochondrial DNA variant, m.14430A>C, in MT-ND6 as the likely cause of Leigh syndrome with mitochondrial complex I deficiency. 1University of Cape Town, Cape Town, South Africa; 2National Health Laboratory Sevices, South Africa; 3Red Cross War Memorial Children's Hospital, Cape Town, South Africa; 4Constantiaberg Mediclinic, Cape Town, South Africa; 5Grootte Schuur Hospital, Cape Town, South Africa; 6Neuroscience Institute, University of Cape Town, Cape Town, South Africa; 7Human Metabolomics, North-West University, Potchefstroom, South Africa Bibliography
Meldau S, Owen EP, Khan K, Riordan GT. “Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings.” J Clin Pathol. 2022 [https://doi.org/10.1136/jclinpath-2020-207026] A.C. Muller-Nedebock, S. Meldau, C. Lombard, S. Abrahams, F.H. van der Westhuizen, S. Bardien, Increased blood-derived mitochondrial DNA copy number in African ancestry individuals with Parkinson's disease Parkinsonism Relat Disord 101 (2022) 1-5. DOI: 10.1016/j.parkreldis.2022.06.003 Meldau S, Fratter C, Bhengu LN, et al. Pitfalls of relying on genetic testing only to diagnose inherited metabolic disorders in non-western populations - 5 cases of pyruvate dehydrogenase deficiency from South Africa. Mol Genet Metab Rep 2020;24:100629 doi: 10.1016/j.ymgmr.2020.100629. Roberts L, Julius S, Dawlat S, Yildiz S, Rebello G, Meldau S, Pillay K, Esterhuizen A, Vorster A, Benefeld G, Da Rocha J, Beighton P, Sellars SL, Thandrayen K, Pettifor JM, Ramesar RS. Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B. Hum Mutat 2020 doi: 10.1002/humu.24094 Meldau, S., De Lacy R, Riordan G, Goddard L, Pillay K, Fieggen K, Marais D, Van der Watt G, “Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy.” Clin Genet, 2018 [PMID:29318572 DOI:10.1111/cge.13208] O’Keefe, H., Queen, R.A., Meldau, S., Lord, P., Elson, J.L. (2018) “Haplogroup context is less important in the penetrance of Mitochondrial DNA complex I mutations compared to mt-tRNA mutations.” J Mol Evol 86:395-403. Ng, Y. S., Lax, N. Z., Maddison, P., Alston, C. L., Blakely, E. L., Hepplewhite, P. D., Riordan, G., Meldau, S., Chinnery, P. F., Pierre, G., Chronopoulou, E., Du, A., Hughes, I., Morris, A. A., Kamakari, S., Chrousos, G., Rodenburg, R. J., Saris, C. G. J., Feeney, C., Hardy, S. A., Sakakibara, T., Sudo, A., Okazaki, Y., Murayama, K., Mundy, H., Hanna, M. G., Ohtake, A., Schaefer, A. M., Champion, M. P., Turnbull, D. M., Taylor, R. W., Pitceathly, R. D. S., McFarland, R. and Gorman, G. S., MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load. EBioMedicine 2018. Meldau, S., G. Riordan, F. Van der Westhuizen, J. L. Elson, I. Smuts, M. S. Pepper and H. Soodyall (2016). "Could we offer mitochondrial donation or similar assisted reproductive technology to South African patients with mitochondrial DNA disease?" S Afr Med J 106(3): 234-236. (Invited editorial) Van der Westhuizen, F. H., P. Z. Sinxadi, C. Dandara, I. Smuts, G. Riordan, S. Meldau, A. N. Malik, M. G. Sweeney, Y. Tsai, G. W. Towers, R. Louw, G. S. Gorman, B. A. Payne, H. Soodyall, M. S. Pepper and J. L. Elson (2015). "Understanding the Implications of Mitochondrial DNA Variation in the Health of Black Southern African Populations: The 2014 Workshop." Hum Mutat 36(5): 569-571. ID: 379
Clinical 1: from new genes to old and novel phenotypes Leigh syndrome and Fanconi renotubular syndrome are the main clinical phenotype due to mutations in NDUFAF6 gene. 1Bambino Gesù Children Hospital, Italy; 2UCL Queen Square Institute of Neurology; 3Université Paris Descartes, Sorbonne Paris Cité ID: 544
Clinical 1: from new genes to old and novel phenotypes Mitochondrial encephalomyopathy associated with the m.618T>C in MT-TF 1Hospital Municipal Dr. José de Carvalho, Brazil; 2Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil ID: 296
Clinical 1: from new genes to old and novel phenotypes TWNK in Parkinson's disease: a Movement Disorder and Mitochondrial Disease Center perspective study 1School of Medicine and Surgery and Milan Center for Neuroscience, University of Milan-Bicocca.; 2Foundation IRCCS San Gerardo dei Tintori, Monza; 3Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy; 4Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Milan, Italy; 5IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 6Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 7Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy; 8Neurology Unit, Rovereto Hospital, Azienda Provinciale per i Servizi Sanitari (APSS) di Trento, Trento, Italy; 9Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Audiology Unit, Milan, Italy; 10University of Milan, Milan, Italy; 11Department of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas, Research Hospital, Milan, Italy; 12Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE 405 30 Gothenburg, Sweden; 13Department of Molecular Medicine, University of Pavia, Pavia, Italy. ID: 394
Clinical 1: from new genes to old and novel phenotypes Novel pathogenic MT-ND3 variant causing a particular MELAS phenotype 1CHU de Nice, France; 2Université Côte d'Azur, CNRS, INSERM, IRCAN; 3Service de Neurologie- Hôpital Pasteur 2, CHU de Nice; 4Centre de référence des Maladies neuromusculaires ID: 474
Clinical 1: from new genes to old and novel phenotypes Mitochondrial molecular genetic findings in the South African diagnostic setting 1University of Cape Town, Cape Town, South Africa; 2National Health Laboratory Sevices, South Africa; 3Red Cross War Memorial Children's Hospital, Cape Town, South Africa Bibliography
Meldau S, Owen EP, Khan K, Riordan GT. “Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings.” J Clin Pathol. 2022 [https://doi.org/10.1136/jclinpath-2020-207026] A.C. Muller-Nedebock, S. Meldau, C. Lombard, S. Abrahams, F.H. van der Westhuizen, S. Bardien, Increased blood-derived mitochondrial DNA copy number in African ancestry individuals with Parkinson's disease Parkinsonism Relat Disord 101 (2022) 1-5. DOI: 10.1016/j.parkreldis.2022.06.003 Meldau S, Fratter C, Bhengu LN, et al. Pitfalls of relying on genetic testing only to diagnose inherited metabolic disorders in non-western populations - 5 cases of pyruvate dehydrogenase deficiency from South Africa. Mol Genet Metab Rep 2020;24:100629 doi: 10.1016/j.ymgmr.2020.100629. Roberts L, Julius S, Dawlat S, Yildiz S, Rebello G, Meldau S, Pillay K, Esterhuizen A, Vorster A, Benefeld G, Da Rocha J, Beighton P, Sellars SL, Thandrayen K, Pettifor JM, Ramesar RS. Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B. Hum Mutat 2020 doi: 10.1002/humu.24094 Meldau, S., De Lacy R, Riordan G, Goddard L, Pillay K, Fieggen K, Marais D, Van der Watt G, “Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy.” Clin Genet, 2018 [PMID:29318572 DOI:10.1111/cge.13208] O’Keefe, H., Queen, R.A., Meldau, S., Lord, P., Elson, J.L. (2018) “Haplogroup context is less important in the penetrance of Mitochondrial DNA complex I mutations compared to mt-tRNA mutations.” J Mol Evol 86:395-403. Ng, Y. S., Lax, N. Z., Maddison, P., Alston, C. L., Blakely, E. L., Hepplewhite, P. D., Riordan, G., Meldau, S., Chinnery, P. F., Pierre, G., Chronopoulou, E., Du, A., Hughes, I., Morris, A. A., Kamakari, S., Chrousos, G., Rodenburg, R. J., Saris, C. G. J., Feeney, C., Hardy, S. A., Sakakibara, T., Sudo, A., Okazaki, Y., Murayama, K., Mundy, H., Hanna, M. G., Ohtake, A., Schaefer, A. M., Champion, M. P., Turnbull, D. M., Taylor, R. W., Pitceathly, R. D. S., McFarland, R. and Gorman, G. S., MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load. EBioMedicine 2018. Meldau, S., G. Riordan, F. Van der Westhuizen, J. L. Elson, I. Smuts, M. S. Pepper and H. Soodyall (2016). "Could we offer mitochondrial donation or similar assisted reproductive technology to South African patients with mitochondrial DNA disease?" S Afr Med J 106(3): 234-236. (Invited editorial) Van der Westhuizen, F. H., P. Z. Sinxadi, C. Dandara, I. Smuts, G. Riordan, S. Meldau, A. N. Malik, M. G. Sweeney, Y. Tsai, G. W. Towers, R. Louw, G. S. Gorman, B. A. Payne, H. Soodyall, M. S. Pepper and J. L. Elson (2015). "Understanding the Implications of Mitochondrial DNA Variation in the Health of Black Southern African Populations: The 2014 Workshop." Hum Mutat 36(5): 569-571. ID: 183
Clinical 1: from new genes to old and novel phenotypes Known genes, new genes and new phenotypes in inherited mitochondrial eye diseases 1Moorfields Eye Hospital NHS Foundation Trust, London, UK; 2Institute of Ophthalmology, University College London, London, UK; 3The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK; 4North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 5John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 6Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK Bibliography
Jurkute N et al. Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches. Eur J Hum Genet. 2018. doi:10.1038/s41431-018-0235-y. PMID: 30143805. Jurkute N et al. SSBP1 mutations in dominant optic atrophy with variable retinal degeneration. Ann Neurol. 2019 Sep;86(3):368-383. doi: 10.1002/ana.25550. Epub 2019 Jul 31. PMID: 31298765. Jurkute N et al. SSBP1-Disease Update: Expanding the Genetic and Clinical Spectrum, Reporting Variable Penetrance and Confirming Recessive Inheritance. Invest Ophthalmol Vis Sci. 2021 Dec 1;62(15):12. doi: 10.1167/iovs.62.15.12. PMID: 34905022. Jurkute N et al. Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature. Invest Ophthalmol Vis Sci. 2021 May 3;62(6):2. doi: 10.1167/iovs.62.6.2. PMID: 33938912. Jurkute N et al. Whole Genome Sequencing Identifies a Partial Deletion of RTN4IP1 in a Patient With Isolated Optic Atrophy. J Neuroophthalmol. 2022 Apr 19. doi: 10.1097/WNO.0000000000001589. PMID: 35439212. Jurkute N et al. Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model. Brain Commun. 2021 Jul 20;3(3):fcab162. doi: 10.1093/braincomms/fcab162. PMID: 34466801. Jurkute N et al. Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype. NPJ Genom Med. 2022 Oct 20;7(1):60. doi: 10.1038/s41525-022-00330-z. PMID: 36266294; PMCID: PMC9581764. Other publications available at: https://pubmed.ncbi.nlm.nih.gov/?term=jurkute. ID: 652
Clinical 1: from new genes to old and novel phenotypes LHON spectrum disorder: new phenotypes and genotypes 1San Raffaele Hospital, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica (Bologna, Italy); 3Studio Oculistico d’Azeglio (Bologna, Italy); 4Department of Clinical Science and Community Health, University of Milan, (Milan, Italy); 5Unit of Neurology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna (Bologna, Italy) ID: 218
Clinical 1: from new genes to old and novel phenotypes Chronic asymmetric progressive external ophthalmoplegia without eyelid weakness Seoul National University Hospital, Korea, Republic of (South Korea) ID: 586
New technological developments and OMICS Bayesian inference enables discovery of functional effects of heteroplasmic mitochondrial mutations in the developing brain Imperial College London, United Kingdom ID: 337
New technological developments and OMICS Cell lineage-specific mitochondrial gene expression is established in the early embryo, prior to organ maturation 1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 3Novo Nordisk Research Centre Oxford, Innovation Building, University of Oxford, Old Road Campus, Oxford, UK; 4Functional Genomics Centre, Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK; 5Max Planck Institute for Biology of Ageing, Cologne, Germany; 6Biosciences Institute, Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK Bibliography
1. Burr et al., Cell, 2023, DOI: 10.1016/j.cell.2023.01.034 ID: 563
New technological developments and OMICS Identifying mitochondrial methyltransferases using unbiased proteome-ligand profiling 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, Sweden; 2Centre of Inherited metabolic diseases, Karolinska University Hospital, Stockholm, Sweden ID: 185
New technological developments and OMICS Engineering mitochondrial aminoacyl-tRNA synthetases as a tool to investigate mitochondrial protein synthesis Newcastle University, United Kingdom Bibliography
Albus CA, Berlinguer-Palmini R, Hewison C, McFarlane F, Savu EA, Lightowlers RN, Chrzanowska-Lightowlers ZM, Zorkau M. Mitochondrial Translation Occurs Preferentially in the Peri-Nuclear Mitochondrial Network of Cultured Human Cells. Biology (Basel). 2021 Oct 15; 10 (10):1050. Zorkau M, Albus CA, Berlinguer-Palmini R, Chrzanowska-Lightowlers ZMA, Lightowlers RN. High-resolution imaging reveals compartmentalization of mitochondrial protein synthesis in cultured human cells. Proc Natl Acad Sci U S A.2021 Feb 9; 118(6):e2008778118. ID: 405
New technological developments and OMICS Short-read NGS for the screening of structural and copy number alterations in mtDNA as powerful diagnostic tool. 1Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, (Munich, Germany); 2Institute of Neurogenomics, Helmholtz Zentrum München (Neuherberg, Germany); 3Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy); 4Department of Neurology, Friedrich-Baur-Institute, LMU Hospital, Ludwig Maximilians University (Munich, Germany); 5Department of Pathophysiology and Transplantation, University of Milan (Milan, Italy) ID: 613
New technological developments and OMICS Ethical dilemmas and diagnostic uplifts; primary mitochondrial disease the era of first line whole genome sequencing 1UCL Queen Square Institute of Neurology, United Kingdom; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK.; 3Centre for Personalised Medicine, and Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; 4Clinical Ethics, Law and Society, Faculty of Medicine, University of Southampton, Southampton, UK Bibliography
(1) Raymond, F. L., Horvath, R. & Chinnery, P. F. First-line genomic diagnosis of mitochondrial disorders. Nat. Rev. Genet. 19, 399–400 (2018). (2) Macken, W. L., Vandrovcova, J., Hanna, M. G. & Pitceathly, R. D. S. Applying genomic and transcriptomic advances to mitochondrial medicine. Nat. Rev. Neurol. 0123456789, (2021). (3) Macken WL et al Mitochondrial DNA variants in genomic data: diagnostic uplifts and predictive implications. Nat Rev Genet. 2021 Sep;22(9):547-548. ID: 506
New technological developments and OMICS Analysis of mitochondrial metabolism using 13C-labeled mass isotopologue analysis and mass spectrometry as a new approach for the diagnostics of mitochondrial disorders 1Department of Genetics, Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands.; 2Department of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboudumc, Nijmegen, The Netherlands Bibliography
Barbosa-Gouveia S, Vázquez-Mosquera ME, Gonzalez-Vioque E, Hermida-Ameijeiras Á, Valverde LL, Armstrong-Moron J, Fons-Estupiña MDC, Wintjes LT, Kappen A, Rodenburg RJ, Couce ML. Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome. Int J Mol Sci. 2021 Dec 15;22(24):13484. doi: 10.3390/ijms222413484. PMID: 34948281; PMCID: PMC8708263. Wintjes LTM, Kava M, van den Brandt FA, van den Brand MAM, Lapina O, Bliksrud YT, Kulseth MA, Amundsen SS, Selberg TR, Ybema-Antoine M, Tutakhel OAZ, Greed L, Thorburn DR, Tangeraas T, Balasubramaniam S, Rodenburg RJT. A novel variant in COX16 causes cytochrome c oxidase deficiency, severe fatal neonatal lactic acidosis, encephalopathy, cardiomyopathy, and liver dysfunction. Hum Mutat. 2021 Feb;42(2):135-141. doi: 10.1002/humu.24137. Epub 2020 Nov 30. PMID: 33169484; PMCID: PMC7898715. ID: 421
New technological developments and OMICS Subcellular metabolomics: a pipeline for compartment-specific metabolic investigations in a mouse model of Leigh syndrome North-West University, South Africa Bibliography
Terburgh K, Lindeque JZ, van der Westhuizen FH, Louw R (2021) Cross‑comparison of systemic and tissue‑specific metabolomes in a mouse model of Leigh syndrome. Metabolomics. 17:101 (IF 4.290 Van der Walt G, Lindeque JZ, Mason S, Louw R (2021) Sub-cellular metabolomics contributes mitochondria-specific metabolic insights to a mouse model of Leigh syndrome. Metabolites 11, 658 (IF 4.932). Terburgh K, Coetzer J, Lindeque JZ, van der Westhuizen FH, Louw R (2021) Aberrant BCAA and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome. BBA Molecular Basis of Disease. 1867 (5) 166082 (IF 4.352). ID: 480
New technological developments and OMICS High‐content screening for modulators of mitochondria‐ER contact sites and identification of their protein targets 1Department of Biology, University of Padova, Italy; 2Department of Biomedical Sciences, University of Padova, Italy ID: 617
New technological developments and OMICS A novel Approach to assess the pathogenicity of mtDNA Variants RadboudUMC, Translational Metabolic Laboratory, Dept of Pediatrics, Nijmegen, The Netherlands ID: 508
New technological developments and OMICS At the core of the apoptotic foci CECAD, Germany ID: 167
New technological developments and OMICS Clinical utility of ultra-rapid genomic testing for infants and children with a suspected mitochondrial disorder 1Murdoch Children's Research Institute, Melbourne, Australia; 2University of Melbourne, Melbourne, Australia; 3Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Australia; 4University of Sydney, Sydney, Australia; 5Australian Genomics, Melbourne, Australia; 6Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia; 7Sydney Children’s Hospitals Network – Westmead, Sydney, Australia; 8Sydney Children’s Hospitals Network – Randwick, Sydney, Australia; 9University of New South Wales, Sydney, Australia; 10Monash Genetics, Monash Health, Melbourne, Australia; 11Department of Paediatrics, Monash University, Melbourne, Australia; 12Paediatric and Reproductive Genetics Unit, Women’s and Children’s Hospital, North Adelaide, Australia; 13Adelaide Medical School, The University of Adelaide, Adelaide, Australia; 14Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, Australia; 15Tasmanian Clinical Genetics Service, Tasmanian Health Service, Hobart, Australia; 16School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; 17Genetic Services of Western Australia, Perth, Australia; 18Department of Clinical Genetics, The Canberra Hospital, Canberra, Australia; 19Centre for Clinical Genetics, Sydney Children's Hospital, Sydney, NSW, Australia; 20Randwick Genomics Laboratory, NSW Health Pathology, Prince of Wales Hospital, Sydney, Australia; 21Neuroscience Research Australia (NeuRA) and Prince of Wales Clinical School, UNSW, Sydney, Australia Bibliography
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St John, M., Thauvin-Robinet, C., Traficante, G., van der Sluijs, P.J., Vergano, S.A., Vos N., Walden, K.K., Azmanov, D., Balci, T., Banka, S., Gecz, J., Henneman, P., Lee, J.A., Mannens, M.M.A.M., Roscioli, T., Siu, V., Amor, D.J., Baynam, G., Bend, E.G., Boycott, K., Brunetti-Pierri, N., Campeau, P.M., Christodoulou, J., Dyment, D., Esber, N. Fahrner, J.A., Fleming M.D., Genevieve, D., Kerrnohan, K.D., McNeill, A., Menke, L.A., Merla, G., Prontera, P., Rockman-Greenberg, C., Schwartz, C., Skinner, S.A., Stevenson, R.E., Vitobello, A., Tartaglia, M., Tedder, M.L., Alders, M., Sadikovic, B. Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders. Human Mutation. 2022: 43(11); 1609-1628. 13.Rius R., Bennett, N.K., Bhattacharya, K., Riley. L.G., Yüksel, Z., Formosa. L.E., Compton, A.G., Dale, R.C., Cowley, M.J., Gayevskiy, V., Al Tala, S., Almehery, A.A., Ryan, M.T., Thorburn, D.R., Nakamura, K., Christodoulou, J. Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy. Human Mut. 2022: 43 (12); 1970-1978. 14.Long, J., Best, S., Nic Giolla Easpaig, B., Hatem, S., Fehlberg, Z., Christodoulou, J., Braithwaite, J. Needs of people with rare diseases that can be supported by electronic resources: a scoping review. Published by BMJ Open 2022 Sep 1;12(9):e060394. doi: 10.1136/bmjopen-2021-060394. 15.Temple, S.E.L., Ho, G., Bennetts, B., Gayagay, T., Boggs, K., Buckley, M., Roscioli, T., Zhu, Y., Mowat, D., Christodoulou, J., Schultz, A., Vidic, N., Lunke, S., Stark, Z., Jaffe,A. The role of exome sequencing in interstitial or diffuse lung disease of childhood. Orphanet J Rare Dis. 2022: 17(1); 350 16.Tudini E, Andrews J, Lawrence D, King-Smith SL, Baker N, Baxter L, Beilby J, Bennetts B, Beshay V, Black M, Boughtwood TF, Brion K, Cheong PL, Christie M, Christodoulou J, Chong B, Cox K, Davis MR, Dejong L, Dinger ME, Doig KD, Douglas E, Dubowsky A, Ellul M, Fellowes A, Fisk K, Fortuno C, Friend K, Gallagher RL, Gao S, Hackett E, Hadler J, Hipwell M, Ho G, Hollway G, Hooper AJ, Kassahn K, Krishnaraj R, Lau C, Le H, Leong HS, Lundie B, Lunke S, Marty A, McPhillips M, Nguyen LT, Nones K, Palmer K, Pearson JV, Quinn MCJ, Rawlings LH, Sadedin S, Sanchez L, Schreiber AW, Sigalas E, Simsek A, Soubrier J, Stark Z, Thompson BA, James U J, Vakulin CG, Wells AV,Wise CA, Woods R, Ziolkowski A, Brion M-J, Scott HS,Thorne NP, Spurdle AB, on behalf of the Shariant Consortium. Shariant platform: enabling evidence sharing across Australian clinical genetic testing laboratories to support variant interpretation. Amer J Human Genet 2022: 109(11); 1960-197. 17.Vogel GF, Mozer-Glassberg Y, Landau YE, Schlieben LD, Prokisch H, Brennenstuhl H, Pechlaner A, Baker JJ, Morrison K, Marina AD, Khan A, Burnyte B, Coman D, Soler-Alfonso C, Scaglia F, Ciara E, M Das AM, Teles EL, Nicastro E, Distelmaier F, Gaignard P, Gonzales E, Baric I, Margolis MG, Christodoulou J, Thorburn DR, Murayama K, Darin N, Pennisi A, Schiff M, Rötig A, Ganetzky RD, Santer R, Konstantopoulou V, Fang W, Wang J-S, McFarland R, Taylor RW, Shagrani MA, Alkuraya FS, Braverman N, Ersoy M Kose M, Feichtinger R, Mayr J, Weghuber D, Wortmann S. Genotypic diversity and phenotypic spectrum of infantile liver failure due to variants in TRMU. Genet Med accepted 26th September 2022. 18.Kline BL, Sylvie Jaillard S, Bell KM, Bakhshalizadeh S, 1 Robevska G, van den Bergen J, Dulon J, Ayers KL, Christodoulou J, Tchan MC, Touraine P, Sinclair AH, Tucker EJ. Integral role of the mitochondrial ribosome in supporting ovarian function: MRPS7 variants in syndromic premature ovarian insufficiency. Genes, accepted 11th November 2022. 19.Neyroud, A.S., Rudinger-Thirion, J., Frugier, M., Riley, L.G., Bidet, M., Akloul, L., Gilot, D., Christodoulou, J., Ravel, C., Sinclair, A.H., Belaud-Rotureau, M-A., Tucker, E.J., Jaillard, S. LARS2 variants can present as isolated premature ovarian insufficiency in the absence of overt hearing loss. Eur J Human Genet, 1 December 2022, Online ahead of print doi: 10.1038/s41431-022-01252-1 ID: 511
New technological developments and OMICS Contribution of RNA-seq to diagnosis and determination of functional impact of candidate variants in 45 patients suspected of mitochondrial disease. 1Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic de Barcelona, IDIBAPS, CIBERER, Barcelona, Spain; 2Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany; 3CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology and Universitat Pompeu Fabra, Barcelona, Spain ID: 560
New technological developments and OMICS Dynamics of NAD and glutathione metabolites in blood during aging, in disease and upon supplementation with NAD-booster 1University of Helsinki, Finland; 2NADMED Ltd, Finland; 3HUS Diagnostic Centre, Finland ID: 446
New technological developments and OMICS Enzymatic assay for UDP-GlcNAc and its application in the parallel assessment of substrate availability and protein O-GlcNAcylation 1Folkhalsan Research Center, Finland; 2Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland; 3Viikki Metabolomics Unit, University of Helsinki, Finland; 4Children’s Hospital, Helsinki University Hospital, Finland ID: 307
New technological developments and OMICS Genetic testing for mitochondrial disease: The United Kingdom best practice guidelines 1NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 2Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 3Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; 4Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Bibliography
PMID: 36513735 PMID: 35700042 PMID: 34732400 ID: 432
New technological developments and OMICS Identification of uncharacterized genes involved in mitochondrial OXPHOS function and integrity. Centro de Biología Molecular Severo Ochoa, Spain ID: 388
New technological developments and OMICS Investigating the role of mito-nuclear genetic variation in determining m.3243A>G variant heteroplasmy 1Wellcome Centre for Mitochondrial Research and Institute for Translational and Clinical Research, Newcastle University, Newcastle upon Tyne, UK; 2NHS Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU Klinikum), Munich, Germany; 4Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 5Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; 6Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; 7Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 8German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 9Department of Neurology, University Hospital Bonn, Bonn, Germany; 10Neurological Institute of Pisa, Italy; 11Institute of Human Genetics, School of Medicine, Technische Universität München, München, Germany; 12Institute of Neurogenomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; 13Department of Neurology, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 14Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany; 15Neurogenetics Unit, The National Hospital for Neurology and Neurosurgery, London, UK; 16Population Health Sciences Institute, Newcastle University, UK ID: 424
New technological developments and OMICS Mitochondrial DNA depletion and deletion analysis using smMIPs 1Translational Metabolic Laboratory, Radboudumc, Nijmegen, The Netherlands; 2Radboud Center for Mitochondrial Medicine (RCMM), Radboudumc, Nijmegen, The Netherlands; 3Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands ID: 513
New technological developments and OMICS Ultrastructure of mitochondria in 3D from volume electron microscopy 1Department of Computer Science, University of Copenhagen, Denmark; 2Center for Quantification of Imaging Data from MAX IV; 3Department of Clinical Medicine, Aarhus University, Denmark; 4Center of Functionally Integrative Neuroscience ID: 304
New technological developments and OMICS Visualizing ATP dynamics in living mice National Cerebral and Cardiovascular Center, Japan ID: 184
New technological developments and OMICS Applying sodium carbonate extraction mass spectrometry to investigate defects in the mitochondrial respiratory chain 1Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Australia; 2Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Australia; 3Department of Biochemistry and Molecular Biology, Monash University, Melbourne,Australia; 4The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 5Baker Heart and Diabetes Institute, Melbourne, Australia; 6Institute for Health and Sport (IHES), Victoria University, Melbourne, Australia Bibliography
[1]Hock D, Robinson D and Stroud D (2020), “Blackout in the powerhouse: clinical phenotypes associated with defects in the assembly of OXPHOS complexes and the mitoribosome”, Biochemical Journal, 477(21):4085-4132. [2]Robinson D, Hock D, Muellner-Wong L, Kugapreethan R, Reljic B, Surgenor E, Rodrigues C, Caruana N and Stroud D (2022), “Applying Sodium Carbonate Extraction Mass Spectrometry to Investigate Defects in the Mitochondrial Respiratory Chain”, Front Cell Dev Biol, 10:786268 ID: 587
New technological developments and OMICS Global analysis of protein methylation in the mitochondrial compartment of cancer cells: a proteomic approach 1Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS Milano, Italy; 2European School of Molecular Medicine (SEMM); 3Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy; 4Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy Bibliography
[1]S.C. Larsen, K.B. Sylvestersen, A. Mund, D. Lyon, M. Mullari, M. V. Madsen, J.A. Daniel, L.J. Jensen, M.L. Nielsen, Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells, Sci. Signal. 9 (2016). https://doi.org/10.1126/SCISIGNAL.AAF7329/SUPPL_FILE/9_RS9_TABLES_S1_TO_S5.ZIP. [2]J.M. Małecki, E. Davydova, P. Falnes, Protein methylation in mitochondria, J. Biol. Chem. 298 (2022). https://doi.org/10.1016/J.JBC.2022.101791. [3]M. Maniaci, F.L. Boffo, E. Massignani, T. Bonaldi, Systematic Analysis of the Impact of R-Methylation on RBPs-RNA Interactions: A Proteomic Approach, Front. Mol. Biosci. 8 (2021) 818. https://doi.org/10.3389/FMOLB.2021.688973/BIBTEX. [4]W. juan Li, Y. hui He, J. jing Yang, G. sheng Hu, Y. an Lin, T. Ran, B. ling Peng, B. lan Xie, M. feng Huang, X. Gao, H. hua Huang, H.H. Zhu, F. Ye, W. Liu, Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth, Nat. Commun. 2021 121. 12 (2021) 1–20. https://doi.org/10.1038/s41467-021-21963-1. [5]V. Spadotto, R. Giambruno, E. Massignani, M. Mihailovich, M. Maniaci, F. Patuzzo, F. Ghini, F. Nicassio, T. Bonaldi, PRMT1-mediated methylation of the microprocessor-associated proteins regulates microRNA biogenesis, Nucleic Acids Res. 48 (2020) 96–115. https://doi.org/10.1093/NAR/GKZ1051. [6]D. Musiani, R. Giambruno, E. Massignani, M.R. Ippolito, M. Maniaci, S. Jammula, D. Manganaro, A. Cuomo, L. Nicosia, D. Pasini, T. Bonaldi, PRMT1 Is Recruited via DNA-PK to Chromatin Where It Sustains the Senescence-Associated Secretory Phenotype in Response to Cisplatin, Cell Rep. 30 (2020) 1208-1222.e9. https://doi.org/10.1016/J.CELREP.2019.12.061/ATTACHMENT/17FA0EA5-8E2C-4786-AFA1-3008203E27DB/MMC5.XLSX. [7]Q. Wu, M. Schapira, C.H. Arrowsmith, D. Barsyte-Lovejoy, Protein arginine methylation: from enigmatic functions to therapeutic targeting, Nat. Rev. Drug Discov. 20 (2021). https://doi.org/10.1038/s41573-021-00159-8. [8]M. Bremang, A. Cuomo, A.M. Agresta, M. Stugiewicz, V. Spadotto, T. Bonaldi, Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome, Mol. Biosyst. 9 (2013) 2231–2247. https://doi.org/10.1039/C3MB00009E. [9]E. Massignani, A. Cuomo, D. Musiani, S.G. Jammula, G. Pavesi, T. Bonaldi, hmSEEKER: Identification of hmSILAC Doublets in MaxQuant Output Data, Proteomics. 19 (2019). https://doi.org/10.1002/PMIC.201800300. [10]E. Massignani, M. Maniaci, T. Bonaldi, Heavy Methyl SILAC Metabolic Labeling of Human Cell Lines for High-Confidence Identification of R/K-Methylated Peptides by High-Resolution Mass Spectrometry, Methods Mol. Biol. 2603 (2023) 173–186. https://doi.org/10.1007/978-1-0716-2863-8_14. ID: 344
New technological developments and OMICS MITODIAG : The French network of diagnostic laboratories for mitochondrial diseases 1Service de génétique médicale, Centre de référence des maladies mitochondriales, CHU Nice, Université Cote d’Azur, CNRS, INSERM, IRCAN, Nice; 2Filnemus, laboratoire de génétique moléculaire, CHU Montpellier; 3Service de génétique, Institut de Biologie en santé, Centre National de référence Maladies Neurodégénératives et Mitochondriales, CHU Angers; 4Fédération de génétique médicale, Service de génétique moléculaire du GH Necker-enfants malades, Hôpital Necker-Enfants Malades, Paris; 5Laboratoire de Biochimie, Pôle BPP, CHU Paris Sud, Hôpital Bicêtre-le Kremlin Bicêtre, Paris; 6Pôle de biologie et pathologie, CHU Bordeaux; 7Unité fonctionnelle d’histologie moléculaire, Service de pathologie, CHU Bordeaux-GU Pellegrin, Bordeaux; 8Service de biochimie et biologie moléculaire Grand Est, UM Maladies Héréditaires du Métabolisme, Centre de biologie et pathologie Est, CHU Lyon HCL, GH Est, Lyon; 9Laboratoire de génétique, Hématologie et Immunologie, CHU Reims; 10Laboratoire de génétique moléculaire: maladies héréditaires et oncologie, Service de biochimie, biologie moléculaire et toxicologie environnementale, CHU Grenoble et des Alpes, Institut de biologie et pathologie, Grenoble; 11Service de biochimie, Pôle Biologie, Pharmacie et Hygiène, CHU Caen, Hôpital de la Côte de Nacre, Caen; 12Laboratoire de Génétique Moléculaire, CHU Montpellier, PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier; 13Filnemus, Assistance Publique Hôpitaux Marseille, Service de Neurologie, Hôpital La Timone, Marseille Bibliography
Claire B, Pauline G, Elise L, Didier E, Geoffroy D, Célia H, Karin M, Anaïs L, Cécile R, Konstantina F, Saadi Samira AE, Christophe P, Ange-Line Christophe B, Laurence F, François F, Warde Marie-Thérèse A.UQCRC2-related mitochondrial complex III deficiency, about 7 patients. Mitochondrion. 2022 Dec 9:S1567-7249(22)00105-2. doi: 10.1016/j.mito.2022.12.001. Ait-El-Mkadem Saadi S., Kaphan E., Jaurrieta A., Fragaki K., Chaussenot A., Bannwarth S., Maues De Paula A., Paquis-Flucklinger V., Rouzier C. Splicing variants in NARS2 are associated with milder phenotypes and intra-familial variability. Eur J Med Genet. 2022 Dec;65(12):104643. doi: 10.1016/j.ejmg.2022.104643. Epub 2022 Oct 14. Bris C, Goudenège D, Desquiret-Dumas V, Gueguen N, Bannwarth S, Gaignard P, Rucheton B, Trimouille A, Allouche S, Rouzier C, Saadi S, Jardel C, Slama A, Barth M, Verny C, Spinazzi M, Cassereau J, Colin E, Armelle M, Pereon Y, Martin-Negrier ML, Paquis-Flucklinger V, Letournel F, Lenaers G, Bonneau D, Reynier P, Amati-Bonneau P, Procaccio V. Improved detection of mitochondrial DNA instability in mitochondrial genome maintenance disorders. Genet Med. 2021 Sep;23(9):1769-1778 Elamine Zereg, Annabelle Chaussenot, Godelieve Morel, Sylvie Bannwarth, Sabrina Sacconi , Marie-Hélène Soriani, Shahram Attarian, Aline Cano, Jean Pouget, Rémi Bellance, Christine Tranchant, Béatrice Lannes, André Maues de Paula, Samira Saadi Ait-El-Mkadem, Bernadette Chafino, Mathieu Berthet, Konstantina Fragaki, Véronique Paquis-Flucklinger, Cécile Rouzier. Single-fiber studies for assigning pathogenicity of eight mitochondrial DNA variants associated with mitochondrial diseases. Hum Mutat . 2020 Aug;41(8):1394-1406. doi: 10.1002/humu.24037. Epub 2020 Jun 12. ID: 331
New technological developments and OMICS Multiomic mitochondrial and metabolic screening reveals potential biomarkers in inclusion body myositis 1Hereditary Metabolic Diseases and Muscular Diseases Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 2Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain; 3CIBERER— Spanish Biomedical Research Centre in Rare Diseases, Madrid, Spain; 4Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu; Esplugues de Llobregat, Barcelona, Spain ID: 465
New technological developments and OMICS Network analysis of protein-protein interactions identifies intermediate filaments as a novel mitochondrial dynamics related structure Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, The Netherlands ID: 170
New technological developments and OMICS Establishment of mitochondrial proline metabolic disorder patient-derived induced pluripotent stem cells as a new cellular model for aging associated disease study Mackay Memorial Hospital, Taiwan Bibliography
Huang YW, Chiang MF, Ho CS, Hung PL, Hsu MH, Lee TH, Chu LJ, Liu H, Tang P, Victor Ng W*, Lin DS*. A Transcriptome Study of Progeroid Neurocutaneous Syndrome Reveals POSTN As a New Element in Proline Metabolic Disorder. Aging Dis 2018;9(6),1043-1057. ID: 659
New technological developments and OMICS Mitochondrial disorders unraveled by NGS technologies 1Research centre for medical genetics, Russian Federation; 2Morozov's Moscow City Child Clinical Hospital, Moscow, Russia Bibliography
Chinnery PF, Hudson G. Mitochondrial genetics. Br Med Bull. 2013;106(1):135-59. doi: 10.1093/bmb/ldt017. Epub 2013 May 22. PMID: 23704099; PMCID: PMC3675899. Rahman J, Rahman S. Mitochondrial medicine in the omics era. Lancet. 2018 Jun 23;391(10139):2560-2574. doi: 10.1016/S0140-6736(18)30727-X. Epub 2018 Jun 18. PMID: 29903433. Legati A, Reyes A, Nasca A, Invernizzi F, Lamantea E, Tiranti V, Garavaglia B, Lamperti C, Ardissone A, Moroni I, Robinson A, Ghezzi D, Zeviani M. New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies. Biochim Biophys Acta. 2016 Aug;1857(8):1326-1335. doi: 10.1016 /j.bbabio.2016.02.022. Epub 2016 Mar 8. PMID: 26968897. ID: 427
New technological developments and OMICS Incorporation of exogenous mitochondria into cells and their effects on the cells 1LUCA Science, Japan; 2Biological Drug Development based DDS technology, Hokkaido Univ. Bibliography
Tateno M., Enami, A., Fujinami K., Ohta H. Polymorphisms in Cha o 1 and Cha o 2, major allergens of Japanese cypress (Chamaecyparis obtuse) pollen from a restricted region in Japan. PLos One 16: e0261327, 2021 Fujimura T, Fujinami K, Ishikawa R, Tateno M, Tahara Y, Okumura Y, Ohta H, Miyazaki H, Taniguchi M. Recombinant Fusion Allergens, Cry j 1 and Cry j 2 from Japanese Cedar Pollen, Conjugated with Polyethylene Glycol Potentiate the Attenuation of Cry j 1-Specific IgE Production in Cry j 1-Sensitized Mice and Japanese Cedar Pollen Allergen-Sensitized Monkeys. Int Arch Allergy Immunol.;168:32-43, 2015 ID: 336
New technological developments and OMICS Mitochondrial encapsulation technology for mitochondrial transplantation therapy 1Pharmaceutical Sciences Laboratory, Åbo Akademi University, Finland; 2Turku Bioscience Centre, University of Turku and Åbo Akademi University ID: 130
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Inhibition of mtDNA transcription in liver reverses diet-induced obesity and hepatosteatosis in the mouse 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden; 2Max-Planck Institute of Biochemistry, Martinsried, Germany; 3Metabolomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany ID: 126
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The mitochondrial phenotype of Leigh syndrome SURF1 mutant patient-derived fibroblasts and recovery using small molecules 1Sheffield Institute for Translational Neuroscience, University of Sheffield, United Kingdom; 2Nanna Therapeutics, Cambridge, United Kingdom ID: 133
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Knockout of Complex III subunit Uqcrh decreases respiratory capacity and impairs cardiac contractile function independent of mitochondrial ROS production 1Institute of Experimental Genetics, German Mouse Clinic, Helmholtz Center Munich, German Research Center for Environmental Health, Germany; 2Jena University Hospital, Friedrich-Schiller University of Jena, Germany; 3Oroboros Instruments, Innsbruck, Austria; 4Department of Biochemistry and Molecular Biology, Semmelweis University Budapest, Hungary; 5Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, Germany; 6Member of German Center for Diabetes Research (DZD), Germany; 7Chair of Experimental Genetics Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, Germany; 8BioMediTech & Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Finland; 9Contributed equally ID: 134
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Molecular insights into the role of complex V deficiency in heart development, function and disease 1Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; 2German Center for Cardiovascular Research (DZHK), partner site Göttingen, Germany; 3Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany; 4Research Group Mitochondrial Structure and Dynamics, Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany Bibliography
1. Pavez-Giani MG and Cyganek L. Recent Advances in Modeling Mitochondrial Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Front Cell Dev Biol. 2022 Jan 10;9:800529. 2. Bomer N*, Pavez-Giani MG*, Grote Beverborg N, Cleland J, van Veldhuisen DJ, van der Meer P. Micronutrient deficiencies in heart failure: mitochondrial dysfunction as a common pathophysiological mechanism? J Intern Med. 2022 Jun;291(6):713-731. 3. Bomer N*, Pavez-Giani MG*, Hoes MF, Deiman FE, Piek A, Simonides W, Boer RA, Berezikov E, Westenbrink D, Silljé HWH, van der Meer P. Identification of DIO2 as a regulator of metabolic reprogramming and mitochondrial function in heart failure. Int J Mol Sci. 2021 Nov 2;22(21):11906. 4. Pavez-Giani MG, Sánchez-Aguilera PI, Bomer N, Miyamoto S, Booij HG, Giraldo P, Oberdorf-Maass SU, Nijholt KT, Yurista SR, Milting H, van der Meer P, Boer RA de, Heller Brown J, Sillje HWH, Westenbrink BD. ATPase Inhibitory Factor-1 Disrupts Mitochondrial Ca2+ Handling and Promotes Pathological Cardiac Hypertrophy through CaMKIIδ. Int J Mol Sci 2021;22. ID: 147
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Establishing mammalian cell models for research of NDUFS1-associated diseases 1Heinrich Heine University Düsseldorf, Germany; 2IUF- Leibniz Research Institute for Environmental Medicine ID: 149
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A neuronal model of mtDNA disease reveals a compensatory reprogramming of the electron transfer chain during neuronal maturation 1Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; 2Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles (UCLA), CA, USA Bibliography
Gorman, G. S. et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Annals of Neurology 77, 753–759 (2015). Russell, O.M., Fruh, I., Rai, P.K. et al. Preferential amplification of a human mitochondrial DNA deletion in vitro and in vivo. Sci Rep 8, 1799 (2018). ID: 156
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Development of mutant mtDNA-targeted TALENs and their application to iPSC-based mitochondrial disease model. Fujita Health University School of Medicine, Japan Bibliography
Yahata, N., Boda, H. and Hata, R. Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs (2021) Mol Ther Methods Clin Dev. 20, 54-68 ID: 165
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Deficits in mitochondrial oxidative phosphorylation enhance SARS-CoV-2 replication 1Children's Hospital of Philadelphia, USA; 2University of Pennsylvania, USA; 3Boston University, USA; 4National Emerging Infectious Diseases Laboratories, Boston, USA ID: 175
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Metabolic analysis of mouse sarcopenic skeletal muscle identifies new strategies to increase lifespan in C. elegans 1Karolinska Institutet, Sweden; 2Centre for Vision Research Duke-NUS & Singapore National Eye Centre, Singapore; 3Save Sight Institute at the University of Sydney, Australia; 4The University of Melbourne, Australia. ID: 181
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Delineating mitochondrial pathology using a genome-wide CRISPR/Cas9 activation screen 1Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH; 2NHS Highly Specialised Rare Mitochondrial Disorders Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE2 4HH ID: 188
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Cancer and cellular senescence – two complementary stress models to study turnover and quality control of mitochondrial respiratory complexes. 1IMol Polish Academy of Sciences, Poland; 2ReMedy International Research Agenda ID: 189
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Proteotoxicity induced mitochondrial integrated stress response in CHCHD10-linked adult-onset spinal muscular atrophy 1Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki; 2Helsinki Institute of Life Science HiLIFE, University of Helsinki; 3Genetically Modified Rodents Unit, Laboratory Animal Center, University of Helsinki; 4Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki; 5Faculty of Biological and Environmental Sciences, University of Helsinki; 6Division of Clinical Neurosciences, Turku University Hospital and University of Turku; 7Department of Neurology, Neuromuscular Research Center, Tampere University Hospital and Tampere University; 8Clinical Neurosciences, Neurology, Helsinki University Hospital Bibliography
1. Harjuhaahto S, Rasila TS, Molchanova SM, Woldegebriel R, Kvist J, Konovalova S, Sainio MT, Pennonen J, Torregrosa-Muñumer R, Ibrahim H, Otonkoski T, Taira T, Ylikallio E, Tyynismaa H (2020) ALS and Parkinson's disease genes CHCHD10 and CHCHD2 modify synaptic transcriptomes in human iPSC-derived motor neurons. Neurobiol Dis. 2020 Jul;141:104940. doi: 10.1016/j.nbd.2020.104940. Epub 2020 May 11. PMID: 32437855. Cover story. 2. Järvilehto J, Harjuhaahto S, Palu E, Auranen M, Kvist J, Zetterberg H, Koskivuori J, Lehtonen M, Saukkonen AM, Jokela M, Ylikallio E, Tyynismaa H (2022) Serum creatine but not neurofilament light is elevated in CHCHD10-linked spinal muscular atrophy. Front. Neurology, 2022. https://doi.org/10.3389/FNEUR.2022.793937 3. Sainio MT, Rasila T, Molchanova SM, Järvilehto J, Torregrosa-Muñumer R, Harjuhaahto S, Pennonen J, Huber N, Herukka S-K Haapasalo A, Zetterberg H, Taira T, Palmio J, Ylikallio E and Tyynismaa H (2022) Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons. Front. Cell Dev. Biol. 2022, 9:820105. doi: 10.3389/fcell.2021.820105 4. Neupane N, Rajendran J, Kvist J, Harjuhaahto S, Hu B, Kinnunen V, Yang Y, Nieminen A I, Tyynismaa H. (2022) Inter-organellar and systemic survival responses to impaired mitochondrial matrix protein import in skeletal muscle. Commun Biol. 2022 Oct 5;5(1):1060. doi: 10.1038/s42003-022-04034-z. 5. Woldegebriel R, Kvist J, White M, Sinkko M, Hänninen S, Sainio MT, Torregrosa-Munumer R, Harjuhaahto S, Huber N, Herukka K, Haapasalo A, Carpen O, Bassett A, Ylikallio E, Sreedharan J, Tyynismaa H. (2021) Peripheral neuropathy linked mRNA export factor GANP 1 reshapes gene regulation in human motor neurons. bioRxiv 2021.05.18.444636. https://doi.org/10.1101/2021.05.18.444636 ID: 190
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Protective role of mitochondrial stress signaling and fragmentation in mitochondrial cardiomyopathy Max Planck Institute for Biology of Ageing, Cologne, Germany ID: 591
Clinical 1: from new genes to old and novel phenotypes The Italian reappraisal on the most frequent genetic defects in hereditary optic neuropathies and the global top 10 1IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 3Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy; 4Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy; 5Ospedale Oftalmico Roma, Rome, Italy; 6Ophthalmology Unit, University Hospital of Parma, Parma, Italy; 7Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; 8Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy; 9Neuroophthalmology Service and Ocular Electrophysiology laboratory, Department of Ophthalmology, IRCCS Istituto Auxologico Italiano, Milan, Italy Bibliography
Rocatcher, Aude et al. “The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands.” Brain : a journal of neurology vol. 146,2 (2023): 455-460. doi:10.1093/brain/awac395 ID: 117
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Aberrant ER-mitochondria communication in human mitochondrial disease 1Columbia University, USA; 2Centro de Investigaciones Biológicas “Margarita Salas”, Madrid, Spain Bibliography
Pera M, Larrea D, Guardia-Laguarta C, Montesinos J, Velasco KR, Chan RB, Di Paolo G, Mehler MF, Perumal GS, Macaluso FP, Freyberg ZZ, Acin-Perez R, Enriquez JA, Schon EA, Area-Gomez E (2017). Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease. EMBO J. 36, 3356-3371. ID: 161
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial F0F1-ATP synthase conditions the responsiveness of mitochondria to fission 1MITOVASC Université d'Angers, France; 2Departments of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France; 3Laboratoire de Neurobiologie et Neuropathologie, Centre Hospitalier Universitaire d'Angers, Angers, France Bibliography
Thirty-year progression of an EMPF1 encephalopathy due to defective mitochondrial and peroxisomal fission caused by a novel de novo heterozygous DNM1L variant 2022 Frontiers neurology PMID: 36212643 DOI: 10.3389/fneur.2022.937885 Glutamate-Induced Deregulation of Krebs Cycle in Mitochondrial Encephalopathy Lactic Acidosis Syndrome Stroke-Like Episodes (MELAS) Syndrome Is Alleviated by Ketone Body Exposure 2022 Biomedicines PMID: 35884972 DOI: 10.3390/biomedicines10071665 STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain 2020 Neuropathology and Applied Neurobiology PMID: 32688444 DOI: 10.1111/nan.12646 Autophagy controls the pathogenicity of OPA1 mutations in dominant optic atrophy 2017 Journal of Cellular and Molecular Medicine PMID: 28378518 DOI: 10.1111/jcmm.13149 ID: 199
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A screening method for mitochondrial disorders by high-resolution respirometry 1National Institute of Chemical Physics and Biophysics, Estonia; 2Clinic of Internal Medicine, East-Tallinn Central Hospital, Estonia Bibliography
1.Tepp, Kersti; Aid-Vanakova, Jekaterina; Puurand, Marju; Timohhina, Natalja; Reinsalu, Leenu; Tein, Karin; Plaas, Mario; Shevchuk, Igor; Terasmaa, Anton; Kaambre, Tuuli; (2022). Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles. Biochemistry and Biophysics Reports, 30, 101250. DOI: 10.1016/j.bbrep.2022.101250. 2. Tepp, Kersti; Puurand, Marju; Timohhina, Natalja; Aid-Vanakova, Jekaterina; Reile, Indrek; Shevchuk, Igor; Chekulayev, Vladimir; Eimre, Margus; Peet, Nadežda; Kadaja, Lumme; Paju, Kalju; Kaambre, Tuuli (2020). Adaptation of mice striated muscles to wolframin deficiency: alterations in cellular bioenergetics. Biochemica et Biophysica Acta. DOI: 10.1016/j.bbagen.2020.129523. 3. Kaup, Karl Kristjan; Toom, Lauri; Truu, Laura; Miller,Sten; Puurand, Marju; Tepp, Kersti; Kaambre Tuuli; Reile, Indrek (2021). A line-broadening free real-time 31P Pure Shift NMR method for phosphometabolomic analysis. The Analyst, 1−5. DOI: 10.1039/D1AN01198G. 4. Rebane-Klemm, Egle; Truu, Laura; Reinsalu, Leenu; Puurand, Marju; Shevchuk, Igor; Chekulayev, Vladimir; Timohhina, Natalja; Tepp, Kersti; Bogovskaja, Jelena; Afanasjev, Vladimir; Suurmaa, Külliki; Valvere, Vahur; Kaambre, Tuuli (2020). Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps. Cancers, 12 (4), ARTN 815. DOI: 10.3390/cancers12040815. ID: 1428
Clinical 1: from new genes to old and novel phenotypes AK3, adenylate kinase isozyme 3, is a new gene associated with PEO and multiple mtDNA deletions 1Fondazione IRCCS Istituto Neurologico Besta, Italy; 2Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Autonomous University of Barcelona, Barcelona, Spain; 3Centro Sclerosi Multipla, P.O. Binaghi, ASL Cagliari, Italy; 4Technical University of Munich, School of Medicine, Institute of Human Genetics, 81675 Munich, Germany; 5Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Munich, Germany; 6Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy ID: 1201
Clinical 1: from new genes to old and novel phenotypes Heterozygous missense variants in NUTF2 (nuclear transport factor 2) gene, mapping at the OPA8 locus, cause Dominant Optic Atrophy 1IRCCS - Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica - Bologna (Italy); 2Studio Oculistico d'Azeglio - Bologna (Italy); 3Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele - Milano (Italy); 4Department of Genetics & Genomics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD-UAM) - Madrid (Spain); 5Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII - Madrid (Spain); 6Grupo de investigación traslacional con células iPS, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red (CIBERER) - Madrid (Spain); 7Université d’Angers, MitoLab team, UMR CNRS 6015 - INSERM U1083, Unité MitoVasc - Angers (France); 8Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, Institute of Genetic Diseases, Imagine and Paris Descartes University - Paris (France); 9Departments of Biochemistry and Genetics, University Hospital Angers - Angers (France); 10Molecular Genetics Laboratory, Institute for Ophthalmic Research, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; 11Depart. of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna - Bologna (Italy) ID: 1348
Clinical 1: from new genes to old and novel phenotypes Southern African paediatric patients with King Denborough syndrome are exclusively associated with an autosomal recessive STAC3 variant: is this a highly prevalent secondary mitochondrial disease in this African population? 1Human Metabolomics, North-West University, Potchefstroom, South Africa; 2Department of Paediatrics, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa; 3Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; 4Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom; 5https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/global-contributor-list Bibliography
Schoonen, M., Smuts, I., Louw, R., Elson, J. L., van Dyk, E., Jonck, L. M., Rodenburg, R. J. T., van der Westhuizen, F. H. (2019). Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease. The Journal of molecular diagnostics 21, 503–513. Meldau, S., Owen, E. P., Khan, K., & Riordan, G. T. (2022). Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings. Journal of clinical pathology 75, 34–38. Reinecke, C. J., Koekemoer, G., van der Westhuizen, F. H., Louw, R., Lindeque, J. Z., Mienie, L. J., Smuts, I. (2012). Metabolomics of urinary organic acids in respiratory chain deficiencies. Metabolomics 8, 264-283. Terburgh, K., Coetzer, J., Lindeque, J. Z., van der Westhuizen, F. H., Louw, R. (2021). Aberrant BCAA and glutamate metabolism linked to regional neurodegeneration in a mouse model of Leigh syndrome. Biochimica et biophysica acta. Molecular basis of disease 1867, 166082. ID: 1356
New technological developments and OMICS Long-read NGS for detection of mitochondrial DNA large-scale deletions and complex rearrangements 1Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy); 2University of Milan (Milan, Italy) ID: 1374
New technological developments and OMICS Quantification of all 12 canonical ribonucleotides by real-time fluorogenic in vitro transcription 1Folkhalsan Research Center, Finland; 2Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki Bibliography
1. Banerjee R, Purhonen J, Kallijärvi J. The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology. FEBS J (2021) 2. Purhonen J, Banerjee R, McDonald AE, Fellman V, Kallijärvi J. A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase. Nucleic Acids Res 48(15), e87 (2020) 3. Purhonen J, Grigorjev V, Ekiert R, Aho N, Rajendran J, Pietras R, Truvé K, Wikström M, Sharma V, Osyczka A, Fellman V, Kallijärvi J. A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice. Nat Commun 11:322 (2020) ID: 1125
New technological developments and OMICS Quantifying mitochondrial proteome remodeling during macrophage polarization University of Lausanne, Switzerland Bibliography
1. C. L. Strelko, et al. J Am Chem Soc. 2011, 133, 16386-16389 2. A. K. Jha, et al. Immunity. 2015, 42, 419-430 3. P. S. Liu, et al. Nat Immunol. 2017, 18, 985-994 4. D. Vats, et al. Cell Metab. 2006, 4, 13-24 5. S. Rath, et al. Nucleic Acids Res. 2021, 49, D1541-D1547 6. A. Michelucci, et al. Proc Natl Acad Sci U S A. 2013, 110, 7820-7825 7. Z. Zhong, et al. Nature. 2018, 560, 198-203 8. S. A. Clayton, et al. Sci Adv. 2021, 7, eabl5182 ID: 158
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial injury in warm ischemia studied by high-resolution respirometry Oroboros Instruments GmBH, Austria ID: 648
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity MitoCluster: integrated phenotyping and mouse model generation platform for mitochondrial disease and dysfunction 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge UK; 3Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, UK; 4NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, UK; 6Cancer Research UK Beatson Institute, Glasgow, UK; 7Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; 8Mary Lyon Centre MRC Harwell, UK; 9University of Padua, Italy |
| 4:30pm - 6:00pm | Session 2.4: New technological developments and OMICS Location: Bologna Congress Center - Sala Europa Session Chair: Holger Prokisch Session Chair: Leonid Sazanov Invited Speaker: :S. Churchman; :H. Hillen |
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ID: 683 Invited Speakers Decoding the regulatory principles of mitochondrial DNA: packaging, expression, and impact on cellular metabolism Harvard Medical School, United States of America Invited
ID: 705 Invited Speakers Mechanisms of mitochondrial RNA biogenesis in health and disease 1Department of Cellular Biochemistry, University Medical Center Göttingen, Germany; 2Research Group Structure and Function of Molecular Machines, Max-Planck-Institute for Multidisciplinary Sciences Göttingen, Germany Bibliography
Bhatta A, Dienemann C, Cramer P, Hillen HS (2021) Structural basis of RNA processing by human mitochondrial RNase P. Nature Structural & Molecular Biology 28, 713-723. Bonekamp NA, Peter B, Hillen HS, Felser A, Bergbrede T, Choidas A, Horn M, Unger A, Di Lucrezia R, Atanassov I, Li X, Koch U, Menninger S, Boros J, Habenberger P, Giavalisco P, Cramer P, Denzel MS, Nussbaumer P, Klebl B, Falkenberg M, Gustafsson CM, Larsson N-G (2020) Small-molecule inhibitors of human mitochondrial DNA transcription. Nature 588, 712-716 Hillen HS, Temiakov D, Cramer P (2018) Structural basis of mitochondrial transcription. Nature Structural & Molecular Biology 25, 754–765 Hillen HS, Parshin AV, Agaronyan K, Morozov YI, Graber JJ, Chernev A, Schwinghammer K, Urlaub H, Anikin M, Cramer P, Temiakov D (2017) Mechanism of Transcription Anti-termination in Human Mitochondria. Cell 171, 1082-1093.e13 Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P (2017) Structural Basis of Mitochondrial Transcription Initiation. Cell 171, 1072-1081.e10 Oral presentation
ID: 338 New technological developments and OMICS Disruption of mitochondrial function induces cell lineage-specific compensatory transcriptional responses during early embryonic development 1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; 3Novo Nordisk Research Centre Oxford, Innovation Building, University of Oxford, Old Road Campus, Oxford, UK; 4Functional Genomics Centre, Milner Therapeutics Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK; 5Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden; 6Max Planck Institute for Biology of Ageing, Cologne, Germany; 7Biosciences Institute, Faculty of Medical Sciences, Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK Bibliography
1. Burr et al., Cell, 2023, DOI: 10.1016/j.cell.2023.01.034 Oral presentation
ID: 120 New technological developments and OMICS Single-cell multi-omics reveals dynamics of purifying selection of pathogenic mitochondrial DNA across human immune cells 1Department of Pathology, Stanford University, Stanford, CA 94305, USA; 2Parker Institute of Cancer Immunotherapy, San Francisco, CA 94129, USA; 3Department of Genetics, Stanford University, Stanford, CA 94305, USA; 4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; 5Division of Hematology / Oncology, Boston Children’s Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; 6Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; 7Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin Institute for Medical Systems Biology (BIMSB), 10115 Berlin, Germany; 8Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany; 9Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, Berlin, Germany; 10Technology Innovation Lab, New York Genome Center, New York, NY 10013, USA; 11Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02134, USA; 12Center for Pediatric Neurosciences, Mitochondrial Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; 13Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; 14Department of Pediatric Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, 13353 Berlin, Germany; 15Department of Computer Science, Stanford University, Stanford, CA 94305, USA; 16Department of Biology and Koch Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; 17Current address: Immunai, New York, NY 10114, USA; 18Current address: 10x Genomics, San Francisco, CA 94111, USA; 19Current address: Genentech, San Francisco, CA 94080, USA Bibliography
Preprint of the manuscript: https://www.biorxiv.org/content/10.1101/2022.11.20.517242v1 Related prior work: https://www.nejm.org/doi/full/10.1056/NEJMoa2001265 https://www.nature.com/articles/s41587-020-0645-6 https://www.nature.com/articles/s41587-021-00927-2 Flash Talk
ID: 125 New technological developments and OMICS Quantifying mitochondrial proteome remodeling during macrophage polarization University of Lausanne, Switzerland Bibliography
1. C. L. Strelko, et al. J Am Chem Soc. 2011, 133, 16386-16389 2. A. K. Jha, et al. Immunity. 2015, 42, 419-430 3. P. S. Liu, et al. Nat Immunol. 2017, 18, 985-994 4. D. Vats, et al. Cell Metab. 2006, 4, 13-24 5. S. Rath, et al. Nucleic Acids Res. 2021, 49, D1541-D1547 6. A. Michelucci, et al. Proc Natl Acad Sci U S A. 2013, 110, 7820-7825 7. Z. Zhong, et al. Nature. 2018, 560, 198-203 8. S. A. Clayton, et al. Sci Adv. 2021, 7, eabl5182 Flash Talk
ID: 374 New technological developments and OMICS Quantification of all 12 canonical ribonucleotides by real-time fluorogenic in vitro transcription 1Folkhalsan Research Center, Finland; 2Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki Bibliography
1. Banerjee R, Purhonen J, Kallijärvi J. The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology. FEBS J (2021) 2. Purhonen J, Banerjee R, McDonald AE, Fellman V, Kallijärvi J. A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase. Nucleic Acids Res 48(15), e87 (2020) 3. Purhonen J, Grigorjev V, Ekiert R, Aho N, Rajendran J, Pietras R, Truvé K, Wikström M, Sharma V, Osyczka A, Fellman V, Kallijärvi J. A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice. Nat Commun 11:322 (2020) Flash Talk
ID: 356 New technological developments and OMICS Long-read NGS for detection of mitochondrial DNA large-scale deletions and complex rearrangements 1Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan, Italy); 2University of Milan (Milan, Italy) |
| 6:00pm - 7:00pm | Poster session Location: Bologna Congress Center Session topics: - Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity |
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ID: 564
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Maintenance on mitochondrial complexes ensures bioenergetic function in differentiated cells 1Institute for Cardiovascular Physiology, Goethe University Frankfurt, Germany; 2Molecular Bioinformatics, Goethe University, Frankfurt, Germany Bibliography
[1] H. Heide, L. Bleier, M. Steger, J. Ackermann, S. Dröse, B. Schwamb, M. Zörnig, A.S. Reichert, I. Koch, I. Wittig, U.Brandt, Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex, Cell Metab. 16 (2012) 538–549. [2] B. Schwanhäusser, M. Gossen, G. Dittmar, M. Selbach, Global analysis of cellular protein translation by pulsed SILAC, Proteomics 9 (2009) 205–209. ID: 462
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Investigating pathogenicity and tissue-specificity of mitochondrial aminoacyl-tRNA synthetase defects AARS2, EARS2 and RARS2 in neurons Department of Clinical Neurosciences, University of Cambridge, United Kingdom ID: 253
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mutations in Coq2 leads to severe developmental delay and early death in both zebrafish and mouse 1Ibs.Granada, Granada, Spain; 2Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 3Biofisika Institute (CSIC,UPV-EHU) and Department of Biochemistry and Molecular Biology, University of Basque Country, Leioa, Spain Bibliography
1.Alcázar-Fabra, M., Rodríguez-Sánchez, F., Trevisson, E., & Brea-Calvo, G. (2021). Primary Coenzyme Q deficiencies: A literature review and online platform of clinical features to uncover genotype-phenotype correlations. Free Radical Biology and Medicine, 167, 141-180. https://doi.org/10.1016/j.freeradbiomed.2021.02.046 2.Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy. (2013). New England Journal of Medicine, 369(3), 233-244. https://doi.org/10.1056/nejmoa1212115 3.Jakobs, B. S., Van Den Heuvel, L. P., Smeets, R., De Vries, M., Hien, S., Schaible, T., Smeitink, J. A., Wevers, R. A., Wortmann, S. B., & Rodenburg, R. J. (2013). A novel mutation in COQ2 leading to fatal infantile multisystem disease. Journal of the Neurological Sciences, 326(1-2), 24-28. https://doi.org/10.1016/j.jns.2013.01.004 4.Herebian, D., Seibt, A., Smits, S. H. J., Rodenburg, R. J., & Mayatepek, E. (2017). 4-Hydroxybenzoic acid restores CoQ10biosynthesis in human COQ2 deficiency. Annals of clinical and translational neurology, 4(12), 902-908. https://doi.org/10.1002/acn3.486 ID: 297
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Pathogenic variants of the mitochondrial metallochaperone SCO1 result in a severe, combined COX and copper deficiency that causes a dilated cardiomyopathy in the murine heart. 1University of Saskatchewan, Canada; 2Auburn University Bibliography
Glerum DM, Shtanko A, Tzagoloff A. Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. J Biol Chem. 1996 Jun 14;271(24):14504-9. doi: 10.1074/jbc.271.24.14504. PMID: 8662933. Srinivasan C, Posewitz MC, George GN, Winge DR. Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae. Biochemistry. 1998 May 19;37(20):7572-7. doi: 10.1021/bi980418y. PMID: 9585572. Hlynialuk CJ, Ling B, Baker ZN, Cobine PA, Yu LD, Boulet A, Wai T, Hossain A, El Zawily AM, McFie PJ, Stone SJ, Diaz F, Moraes CT, Viswanathan D, Petris MJ, Leary SC. The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis. Cell Rep. 2015 Feb 17;10(6):933-943. doi: 10.1016/j.celrep.2015.01.019. Epub 2015 Feb 13. PMID: 25683716. Baker ZN, Jett K, Boulet A, et al. The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart. Hum Mol Genet. 2017;26(23):4617-4628. doi:10.1093/hmg/ddx344 Leary, S.C., Antonicka, H., Sasarman, F., Weraarpachai, W., Cobine, P.A., Pan, M., Brown, G.K., Brown, R., Majewski, J., Ha, K.C.H., et al. (2013a). Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic acidosis. Hum. Mutat. 34, 1366–1370. ID: 196
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Tissue-specific adaptation of stress responses upon COX10 deficiency 1CECAD Research Center, Germany; 2Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne ID: 269
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Using iPSC-derived neurons to unravel the pathomechanisms of Leber’s hereditary optic neuropathy 1Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 3Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy; 4National Research Council (CNR), Institute of Neuroscience, Milan, Italy; 5Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies, University of Ferrara, 44121 Ferrara, Italy; 6Maria Cecilia Hospital, GVM Care & Research, 48033, Cotignola, Ravenna, Italy; 7Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy Bibliography
Danese A, Patergnani S, Maresca A, Peron C, Raimondi A, Caporali L, Marchi S, La Morgia C, Del Dotto V, Zanna C, Iannielli A, Segnali A, Di Meo I, Cavaliere A, Lebiedzinska-Arciszewska M, Wieckowski MR, Martinuzzi A, Moraes-Filho MN, Salomao SR, Berezovsky A, Belfort R Jr, Buser C, Ross-Cisneros FN, Sadun AA, Tacchetti C, Broccoli V, Giorgi C, Tiranti V, Carelli V, Pinton P. Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy. Cell Rep. 2022 Jul 19;40(3):111124. doi: 10.1016/j.celrep.2022.111124. PMID: 35858578; PMCID: PMC9314546. Peron C, Maresca A, Cavaliere A, Iannielli A, Broccoli V, Carelli V, Di Meo I, Tiranti V. Exploiting hiPSCs in Leber's Hereditary Optic Neuropathy (LHON): Present Achievements and Future Perspectives. Front Neurol. 2021 Jun 8;12:648916. doi: 10.3389/fneur.2021.648916. PMID: 34168607; PMCID: PMC8217617. Peron C, Mauceri R, Cabassi T, Segnali A, Maresca A, Iannielli A, Rizzo A, Sciacca FL, Broccoli V, Carelli V, Tiranti V. Generation of a human iPSC line, FINCBi001-A, carrying a homoplasmic m.G3460A mutation in MT-ND1 associated with Leber's Hereditary optic Neuropathy (LHON). Stem Cell Res. 2020 Oct;48:101939. doi: 10.1016/j.scr.2020.101939. Epub 2020 Aug 3. PMID: 32771908. ID: 418
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Stem cell modelling of mitochondrial disease-linked cardiomyopathy 1Murdoch Children’s Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia; 2Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia; 3Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia; 4Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia; 5Victorian Clinical Genetics Services, The Royal Children’s Hospital, Melbourne, VIC, Australia; 6The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; 7Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia; 8Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Melbourne, VIC, Australia ID: 316
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Biochemical and computational approaches to dissect the effect of MT-CYB pathogenic mutations on respiratory chain activity and assembly Department of Pharmacy and Biotechnology, University of Bologna, Italy Bibliography
1 Fernández-Vizarra E, Ugalde C. Cooperative assembly of the mitochondrial respiratory chain. Trends Biochem Sci. 2022 2 Rugolo M, Zanna C, Ghelli AM. Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences. Life (Basel). 2021 3 Mishra SK. PSP-GNM: Predicting Protein Stability Changes upon Point Mutations with a Gaussian Network Model. Int J Mol Sci. 2022 ID: 565
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Exploring the assembly and maintenance of mitochondrial complex I by complexome profiling-based approaches 1Institute for Cardiovascular Physiology, Goethe University Frankfurt, Germany; 2Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands Bibliography
[1] S. Guerrero-Castillo, F. Baertling, D. Kownatzki, H.J. Wessels, S. Arnold, U. Brandt, L. Nijtmans, The Assembly Pathway of Mitochondrial Respiratory Chain Complex I, Cell metabolism, 25 (2017) 128-139. [2] H. Heide, L. Bleier, M. Steger, J. Ackermann, S. Drose, B. Schwamb, M. Zornig, A.S. Reichert, I. Koch, I. Wittig, U. Brandt, Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex, Cell metabolism, 16 (2012) 538-549. [3] A. Cabrera-Orefice, A. Potter, F. Evers, J.F. Hevler, S. Guerrero-Castillo, Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease, Front Cell Dev Biol, 9 (2022) 796128. ID: 225
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Functional involvement of actin-binding Gelsolin on mitochondrial Oxphos dysfunction Fundación Hospital 12 de Octubre, Spain Bibliography
García-Bartolomé, A., Peñas, A., Illescas, M., Bermejo, V., López-Calcerrada, S., Pérez-Pérez, R., et al. (2020). Altered Expression Ratio of Actin-Binding Gelsolin Isoforms Is a Novel Hallmark of Mitochondrial OXPHOS Dysfunction. Cells 9, 1922–21. doi:10.3390/cells9091922 Peñas, A., Fernández-De la Torre, M., Laine-Menéndez, S., Lora, D., Illescas, M., García-Bartolomé, A., et al. (2021). Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders. Ijms 22, 6396. doi:10.3390/ijms22126396 Illescas M, Peñas A, Arenas J, Martín MA and Ugalde C. 2021. Regulation of Mitochondrial Function by the Actin Cytoskeleton. Front. Cell Dev. Biol. 9:795838. doi: 10.3389/fcell.2021.795838. Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C. 2022 Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. doi: 10.1016/j.cmet.2022.09.005 ID: 472
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity In vivo role of respiratory complex I NDUFA10 subunit in dNTP homeostasis 1Research Group on Neuromuscular and Mitochondrial Disorders, Vall d’Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; 2Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; 3BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), University of Barcelona, Barcelona 08028, Spain. and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain.; 4Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia; 5Instituto de Investigación, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041 Madrid, Spain.; 6Laboratory of Metabolism and Obesity, Vall d'Hebron - Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERDEM, CIBER on Diabetes and Associated Metabolic Diseases, Instituto de Salud Carlos III, Barcelona, Spain Bibliography
Molina-Granada D, González-Vioque E, Dibley MG, Cabrera-Pérez R, Vallbona-Garcia A, Torres-Torronteras J, Sazanov LA, Ryan MT, Cámara Y, Martí R. Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Commun Biol. 2022 Jun 23;5(1):620. doi: 10.1038/s42003-022-03568-6. PMID: 35739187; PMCID: PMC9226000. ID: 247
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Modeling POLRMT pathogenic variants in the mouse 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden; 3Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden ID: 425
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The role of the CCR4 family member ANGEL1 in the expression of mitochondrial-targeted proteins 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden Bibliography
Chang, K§., Liu, P§., Requejo, G & Bai, H. (2022). mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila. Front. Cell Dev. Biol., 2022. https://doi.org/10.3389/fcell.2022.866210 §These authors contributed equally to this work Birnbaum, A., Chang, K., & Bai, H. (2020). FOXO regulates neuromuscular junction homeostasis during Drosophila aging. Front Aging Neurosci, 2021 Jan 27; 12:567861. DOI: 10.3389/fnagi.2020.567861. Huang, K., Miao, T., Chang, K. et al. Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine. Nat Commun 11, 2943 (2020). https://doi.org/10.1038/s41467-020-16781-w Kai Chang§, Ping Kang§, Ying Liu, Kerui Huang, Ting Miao, Antonia P. Sagona, Ioannis P. Nezis, Rolf Bodmer, Karen Ocorr & Hua Bai (2019) TGFB-INHB/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2, Autophagy, DOI: 10.1080/15548627.2019.1704117 §These authors contributed equally to this work Kang, P., Chang, K., Liu, Y. et al. Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO. Sci Rep 7, 16369 (2017) doi:10.1038/s41598-017-16638-1 ID: 600
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Tissue-specific bioenergetics in mouse models of mitochondrial disease 1Università di Padova; 2Semmelweis University; 3Universität Innsbruck; 4University of Sussex ID: 490
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Yeast as a tool to investigate variants in mtARS genes associated with mitochondrial diseases 1Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; 2Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 3Department of Medical Physiopathology and Transplantation, University of Milan, Milan, Italy ID: 227
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A mutation in mouse mt-Atp6 gene induces respiration defects and opposed effects on the cell tumorigenic phenotype 1University of Zaragoza, Spain; 2University of Zaragoza, Peaches Biotech Group, Spain; 3Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Spain Bibliography
1.Moreno-Loshuertos, R.; Marco-Brualla, J.; Meade, P.; Soler-Agesta, R.; Enriquez, J. A.; Fernandez-Silva, P., How hot can mitochondria be? Incubation at temperatures above 43 degrees C induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria. Mitochondrion 2023, 69, 83-94. 2.Moreno-Loshuertos, R.; Movilla, N.; Marco-Brualla, J.; Soler-Agesta, R.; Ferreira, P.; Enriquez, J. A.; Fernandez-Silva, P., A Mutation in Mouse MT-ATP6 Gene Induces Respiration Defects and Opposed Effects on the Cell Tumorigenic Phenotype. Int J Mol Sci 2023, 24, (2). 3.Novo, N.; Romero-Tamayo, S.; Marcuello, C.; Boneta, S.; Blasco-Machin, I.; Velázquez-Campoy, A.; Villanueva, R.; Moreno-Loshuertos, R.; Lostao, A.; Medina, M.; Ferreira, P., Beyond a platform protein for the degradosome assembly: The Apoptosis-Inducing Factor as an efficient nuclease involved in chromatinolysis. PNAS Nexus 2022, 2, (2). 4.Soler-Agesta, R.; Marco-Brualla, J.; Minjarez-Saenz, M.; Yim, C. Y.; Martinez-Julvez, M.; Price, M. R.; Moreno-Loshuertos, R.; Ames, T. D.; Jimeno, J.; Anel, A., PT-112 Induces Mitochondrial Stress and Immunogenic Cell Death, Targeting Tumor Cells with Mitochondrial Deficiencies. Cancers (Basel) 2022, 14, (16). 5.Pinol, R.; Zeler, J.; Brites, C. D. S.; Gu, Y.; Tellez, P.; Carneiro Neto, A. N.; da Silva, T. E.; Moreno-Loshuertos, R.; Fernandez-Silva, P.; Gallego, A. I.; Martinez-Lostao, L.; Martinez, A.; Carlos, L. D.; Millan, A., Real-Time Intracellular Temperature Imaging Using Lanthanide-Bearing Polymeric Micelles. Nano Lett 2020, 20, (9), 6466-6472. 6.Gu, Y.; Yoshikiyo, M.; Namai, A.; Bonvin, D.; Martinez, A.; Pinol, R.; Tellez, P.; Silva, N. J. O.; Ahrentorp, F.; Johansson, C.; Marco-Brualla, J.; Moreno-Loshuertos, R.; Fernandez-Silva, P.; Cui, Y.; Ohkoshi, S. I.; Millan, A., Magnetic hyperthermia with epsilon-Fe(2)O(3) nanoparticles. RSC Adv 2020, 10, (48), 28786-28797. 7.Delavallee, L.; Mathiah, N.; Cabon, L.; Mazeraud, A.; Brunelle-Navas, M. N.; Lerner, L. K.; Tannoury, M.; Prola, A.; Moreno-Loshuertos, R.; Baritaud, M.; Vela, L.; Garbin, K.; Garnier, D.; Lemaire, C.; Langa-Vives, F.; Cohen-Salmon, M.; Fernandez-Silva, P.; Chretien, F.; Migeotte, I.; Susin, S. A., Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus. Mol Metab 2020, 40, 101027. ID: 242
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A systemic Muscle-WAT crosstalk progressively depletes protein and fat stores aggravating mitochondrial myopathy. 1Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY; 2Weill Cornell Medicine, Department of Pharmacology, New York, NY; 3Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy. ID: 646
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A novel mitochondrial assembly factor RTN4IP1 has an essential role in the final stages of Complex I assembly 1Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 2Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK; 3Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; 4Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; 5Functional Proteomics Group, Institute for Cardiovascular Physiology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany Bibliography
1 Charif M et al. Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults. JAMA Neurol. 2017 ID: 599
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity ETFDH supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis 1Department of Molecular Biology, Centro de Biología Molecular "Severo Ochoa" (CBMSO-UAM-CSIC), Madrid, Spain; 2Instituto Universitario de Biología Molecular (IUBM), Autonomous University of Madrid, Madrid, Spain; 3Centro de Investigación Biomédica en red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain; 4Instituto de Investigación Hospital 12 de octubre, i+12, Universidad Autónoma de Madrid, Madrid, Spain ID: 559
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Metabolic rewiring as an adaptive mechanism in COX null cells 1Department of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 2Faculty of Science, Charles University, 12800 Prague, Czech Republic; 3Laboratory of Translational Metabolomics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic ID: 383
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Metabolic rewiring due to progressive increase in mtDNA mutation heteroplasmy reveals markers of disease severity 1North-West University, South Africa; 2Osaka University, Japan; 3Radboud University Medical Center, Netherlands; 4University of Tsukuba, Japan ID: 442
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Novel or rare AIFM1 pathogenic variants: their impact on mitochondrial metabolism and clinical manifestation in eight patients, including 3 girls 1Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague; 2Institute of Molecular and Clinical Pathology and Medical Genetics, University Hospital Ostrava ID: 558
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Pathological molecular mechanisms underlying COA8 loss of function 1Department of Biomedical Sciences, University of Padova, Padova, Italy; 2Veneto Institute of Molecular Medicine, Padova, Italy; 3Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; 4University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Department of Chemical Sciences, University of Padova, Padova, Italy; 6Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; 7Department of Neurosciences, University of Padova, Padova, Italy Bibliography
Hedberg-Oldfors, C., Darin, N., Thomsen, C., Lindberg, C., and Oldfors, A. (2020). COX deficiency and leukoencephalopathy due to a novel homozygous APOPT1/COA8 mutation. Neurol Genet 6, e464. Melchionda, L., Haack, T.B., Hardy, S., Abbink, T.E., Fernandez-Vizarra, E., Lamantea, E., Marchet, S., Morandi, L., Moggio, M., Carrozzo, R., et al. (2014). Mutations in APOPT1, Encoding a Mitochondrial Protein, Cause Cavitating Leukoencephalopathy with Cytochrome c Oxidase Deficiency. Am J Hum Genet 95, 315-325. Pei, J., Zhang, J., and Cong, Q. (2022). Human mitochondrial protein complexes revealed by large-scale coevolution analysis and deep learning-based structure modeling. Bioinformatics. Sharma, S., Singh, P., Fernandez-Vizarra, E., Zeviani, M., Van der Knaap, M.S., and Saran, R.K. (2018). Cavitating Leukoencephalopathy With Posterior Predominance Caused by a Deletion in the APOPT1 Gene in an Indian Boy. J Child Neurol 33, 428-431. Signes, A., Cerutti, R., Dickson, A.S., Beninca, C., Hinchy, E.C., Ghezzi, D., Carrozzo, R., Bertini, E., Murphy, M.P., Nathan, J.A., et al. (2019). APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS. EMBO molecular medicine 11. ID: 366
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Retinal pathophysiology characterisation of the novel mitochondrial heteroplasmy mouse model 1University of Cambridge, United Kingdom; 2Newcastle University, United Kingdom ID: 666
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Impaired spermatogenesis driven by mitochondrial dysfunction and ferroptosis in primary spermatocytes in a mouse model of Leigh syndrome 1University of Pennsylvania,USA; 2University of Angers, SFR ICAT, SCIAM, 49000 Angers, France; 3MITOLAB, University of Angers, INSERM U1083, France; 4Pablo de Olavide University, Spain; 5Neuromuscular Reference Center CHU Angers, France ID: 574
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitophagy dysfunction in mitochondrial myopathy and therapy by mitophagy activator CAP1902 1STEMM Research Program, Biomedicum Helsinki, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 3Department of Pharmacology, Center for Innovations in Brain Science, University of Arizona, Tucson, AZ, USA; 4Department of Medicine, Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA ID: 192
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mtfp1 controls oxidative phosphorylation and cell death in liver disease 1Institut Pasteur, Mitochondrial Biology Group, CNRS UMR 3691, Université Paris Cité, Paris, France.; 2Institut Pasteur, Biomics Technological Platform, Université Paris Cité, Paris, France.; 3Institut Pasteur, Bioinformatics and Biostatistics Hub, Université Paris Cité, Paris, France.; 4Institut Pasteur, Proteomics Core Facility, MSBio UtechS, UAR CNRS 2024, Université Paris Cité, Paris, France.; 5Institut Pasteur Ultrastructural Bio Imaging, UTechS, Université Paris Cité, Paris, France.; 6Platform for Metabolic Analyses, SFR Necker, INSERM US24/CNRS UMS 3633, Paris, France.; 7Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia. ID: 319
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Non-canonical function of succinate dehydrogenase assembly factor 2 (SDHAF2) during OXPHOS dysfunction 1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia; 2Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; 3Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia; 4Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia; 5Victorian Clinical Genetics Services, Royal Children's Hospital, Parkville, VIC, Australia ID: 502
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity NUAK1-dependent metabolic underpinnings of adult muscle stem cells Physiopathology and Genetics of Neurons and Muscles Laboratory, Institut NeuroMyoGène, Lyon, France ID: 415
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity A novel approach to measure complex V ATP hydrolysis in frozen cell lysates and tissue homogenates 1Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095 USA; 2Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA; 3Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA; 4Molecular & Cellular Integrative Physiology, University of California, Los Angeles, CA, 90095, USA.; 5Institut de Biologia Molecular de Barcelona, IBMB-CSIC, Barcelona, Catalonia, 08028, Spain ID: 440
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity OxPhos defects cause cell-autonomous and whole-body signs of hypermetabolism in cells and in patients with mitochondrial diseases 1Columbia University Irving Medical Center, United States of America; 2University of Florida, United States of America; 3Angers University, UMR CNRS 6015 - INSERM U1083, MitoVasc Institute, Angers, France; 4Yale University, United States of America; 5University of Pennsylvania, United States of America; 6Stanford University, United States of America; 7University of California San Francisco, United States of America; 8Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 9University of Copenhagen, Denmark; 10University of Udine, Italy; 11Altos labs, United States of America; 12University of Texas Southwestern Medical Center, United States of America; 13University of Pittsburgh, United States of America; 14Thomas Jefferson University, United States of America Bibliography
Sturm G et al. A multi-omics longitudinal aging dataset in primary human fibroblasts with mitochondrial perturbations. Sci Data 9, 751 (2022). https://doi.org/10.1038/s41597-022-01852-y Sturm G. et al. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Commun Biol 6, 22 (2023). https://doi.org/10.1038/s42003-022-04303-x ID: 605
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Dysfunction of mitochondrial chaperone HSP60 triggers disruption of mitochondrial pathways activating multiple regulatory responses 1Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark; 3Department of Forensic Medicine, Aarhus University, Aarhus, Denmark; 4Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Bibliography
1. Bie AS, Cömert C, Körner R, et al. An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. Cell Stress Chaperones. 2020;25(3):407-416. 2. Bross P, Naundrup S, Hansen J, et al. The Hsp60-(p.V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo. J Biol Chem. 2008;283(23):15694-15700. 3. Magen D, Georgopoulos C, Bross P, et al. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet. 2008;83(1):30-42. 4. Cömert C, Brick L, Ang D, et al. A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy. Cold Spring Harb Mol Case Stud. 2020;6(3):a004879. Published 2020 Jun 12. ID: 365
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Generation of iPSCs derived neural progenitors and cardiomyocytes as cellular models to study the pathophysiology of Pearson Syndrome 1Unit of Medical genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 2Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy; 3Department of Biotechnology and Biosciences, University of Milano - Bicocca, Milan, Italy ID: 476
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity High aerobic exercise capacity predicts increased mitochondrial response to exercise training 1Department of Cardiothoracic Surgery, University Hospital of Friedrich-Schiller-University Jena, Germany; 2Department of Physiology and Pharmacology, University of Toledo, Toledo, OH, United States; 3Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States Bibliography
Heyne E, Schrepper A, Doenst T, Schenkl C, Kreuzer K, Schwarzer M. High-fat diet affects skeletal muscle mitochondria comparable to pressure overload-induced heart failure. J Cell Mol Med. 2020 Jun;24(12):6741-6749. doi: 10.1111/jcmm.15325. Epub 2020 May 4. PMID: 32363733; PMCID: PMC7299710. Schwarzer M, Molis A, Schenkl C, Schrepper A, Britton SL, Koch LG, Doenst T. Genetically determined exercise capacity affects systemic glucose response to insulin in rats. Physiol Genomics. 2021 Sep 1;53(9):395-405. doi: 10.1152/physiolgenomics.00014.2021. Epub 2021 Jul 23. PMID: 34297615; PMCID: PMC8530732. ID: 488
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Investigating the role of LONP1 in heart and skeletal muscle metabolism 1Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 50931 Cologne, Germany; 2Department III of Internal Medicine, Heart Center, University Hospital of Cologne, 50931 Cologne, Germany; 3Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany ID: 229
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial dysfunction promotes liver fibrosis through the ACOT2-MCT6-OXCT1 axis. 1Karolinska Institutet, Sweden; 2Zhengzhou University, China; 3Norwegian Veterinary Institute, Norway Bibliography
Zhou X, Mikaeloff F, Curbo S, Zhao Q, Kuiper R, Végvári Á, Neogi U, Karlsson A.Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.Hum Mol Genet. 2021 Oct 13;30(21):2012-2026 ID: 655
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity PNC2 (SLC25A36) deficiency associated with the hyperinsulinism/hyperammonemia syndrome 1Università degli Studi di Bari Aldo Moro, Italy; 2Libera Università Mediterranea Giuseppe Degennaro, Italy; 3Department of Pediatrics and Genetics, Al Makassed Hospital and Al-Quds University, Palestine.; 4Department of Genetics, Hadassah, Hebrew University Medical Center, Israel Bibliography
[1] M.A. Shahroor, F.M. Lasorsa, V. Porcelli V, I. Dweikat, M.A. Di Noia, M. Gur, G. Agostino, A . Shaag A, T. Rinaldi, G. Gasparre, F. Guerra, A. Castegna, S. Todisco, B. Abu-Libdeh, O. Elpeleg, L. Palmieri, PNC2 (SLC25A36) Deficiency Associated With the Hyperinsulinism/Hyperammonemia Syndrome, J Clin Endocrinol Metab, 107(2022):1346-1356. [2] L. Jasper, P. Scarcia, S. Rust, J. Reunert, F. Palmieri, T. Marquardt, Uridine Treatment of the First Known Case of SLC25A36 Deficiency, Int J Mol Sci. 22(2021) 9929. [3] Safran A, Proskorovski-Ohayon R, Eskin-Schwartz M, Yogev Y, Drabkin M, Eremenko E, Aharoni S, Freund O, Jean MM, Agam N, Hadar N, Loewenthal N, Staretz-Chacham O, Birk OS.Hyperinsulinism/hyperammonemia syndrome caused by biallelic SLC25A36 mutation. J Inherit Metab Dis. 2023 Jan 25. doi: 10.1002/jimd.12594. Online ahead of print ID: 397
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Cultured neurons with CoQ10 deficiency reveal alterations of lipid metabolism 1Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10032, United States; 2IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 3Institute of Biotechnology, Biomedical Research Center (CIBM), Health Science Technological Park (PTS), University of Granada, Armilla, Granada, 18100, Spain; 4Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE; 5Unita` di Genetica delle Malattie Neurodegenerative e Metaboliche, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, 20126, Italy Bibliography
1. Turunen, M.; Olsson, J.; Dallner, G. Metabolism and function of coenzyme Q. Biochim. Biophys. Acta - Biomembr. 2004, 1660, 171–199, doi:10.1016/j.bbamem.2003.11.012. 2. Quinzii, C.M.; López, L.C.; Gilkerson, R.W.; Dorado, B.; Coku, J.; Naini, A.B.; Lagier-Tourenne, C.; Schuelke, M.; Salviati, L.; Carrozzo, R.; et al. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J. 2010, 24, 3733–3743, doi:10.1096/fj.09-152728. 3. Emma, F.; Montini, G.; Parikh, S.M.; Salviati, L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. 2016, doi:10.1038/nrneph.2015.214. 4. Ernster, L.; Dallner, G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta 1995, 1271, 195–204. ID: 426
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration 1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland; 2Biocenter Oulu, University of Oulu, Oulu, Finland; 3Faculty of Physics, University of Warsaw, Warsaw, Poland; 4Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany; 5Department of Biochemistry and Molecular Biology, University of Würzburg, Würzburg, Germany; 6Zentrum für Molekulare Biologie (ZMBH), DKFZ-ZMBH Alliance and Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany Bibliography
Rahman M.T., Koski M.K., Panecka-Hofman J., Schmitz W, Kastaniotis A.J., Wade R.C., Wierenga R.K., Hiltunen J.K. & Autio K.J. (2023) An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration. Nature Communications 14(1):619. doi: 10.1038/s41467-023-36358-7 Alam J., Sah-Teli S.K., Venkatesan R., Koski M.K., Autio K.J., Hiltunen J K. & Kastaniotis A.J. (2021) Biophysical and structural analysis of the SAM-dependent Saccharomyces cerevisiae methyltransferase family protein Rsm22. Acta Crystallographica Section D. 77:840-853 Kastaniotis A.J., Autio K.J. & Nair R.R. (2021) Mitochondrial fatty acids and neurodegenerative disorders. Neuroscientist 27(2):143-158 ID: 561
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Antibiotics directly affect mitochondrial respiration 1Technische Universität München, Germany; 2Oroboros Instruments GmbH, Innsbruck, Austria; 3Helmholtz Zentrum München, Germany Bibliography
[1] Tarantino G. et al. (2017): Hepatol Res. 37:410‐415 [2] O'Reilly M. et al. (2019):. Front Cell Neurosci. 13;13:416. doi: 10.3389/fncel.2019.00416. [3] Oyebode OT. et al. (2018) Toxicology Mechanisms and Methods, 1–31.doi:10.1080/15376516.2018.1528651 ID: 471
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Can transmission of mitochondria over the species barrier promote climate change adaptation? 1Tampere University, Finland; 2University of Eastern Finland Bibliography
Gaertner K, Michell C, Tapanainen R, et al. Molecular phenotyping uncovers differences in basic housekeeping functions among closely related species of hares (Lepus spp., Lagomorpha: Leporidae) [published online ahead of print, 2022 Nov 1]. Mol Ecol. 2022; doi:10.1111/mec.16755 ID: 626
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Developing an in vitro model to study the impact of the m.3243A>G mutation in iPSC-derived myofibers University College London, United Kingdom ID: 334
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Discordant phenotype in fibroblast cell lines generated from the same MELAS patient 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and Neuromuscular Sciences (DIBINEM), University of Bologna ID: 531
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Generation of a novel CoQ deficient mouse model to elucidate the role of COQ4 Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA. Bibliography
1.Guerra, R.M. and D.J. Pagliarini, Coenzyme Q biochemistry and biosynthesis. Trends Biochem Sci, 2023. 2.Alcázar-Fabra, M., E. Trevisson, and G. Brea-Calvo, Clinical syndromes associated with Coenzyme Q. Essays Biochem, 2018. 62(3): p. 377-398. 3.Belogrudov, G.I., et al., Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis. Arch Biochem Biophys, 2001. 392(1): p. 48-58. 4.Casarin, A., et al., Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis. Biochem Biophys Res Commun, 2008. 372(1): p. 35-9. 5.Marbois, B., et al., Coq3 and Coq4 define a polypeptide complex in yeast mitochondria for the biosynthesis of coenzyme Q. J Biol Chem, 2005. 280(21): p. 20231-8. 6.Marbois, B., et al., The yeast Coq4 polypeptide organizes a mitochondrial protein complex essential for coenzyme Q biosynthesis. Biochim Biophys Acta, 2009. 1791(1): p. 69-75. ID: 414
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Perivascular adipose tissue remodeling impairs mitochondrial function in thermoneutral-housed rats 1University of Colorado/Rocky Mountain Regional VA Medical Center, United States of America; 2Cornell College, United States of America Bibliography
1. Chun J.H., Henckel M.M., Knaub L.A., Hull S.E., Pott G.B., Ramirez D.G., Reusch J.E.-B., Keller A.C. (-)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality. Planta Med. 2022 Aug;88(9-10):735-744. doi: 10.1055/a-1843-9855. 2. Keller A.C., Chun J.H., Knaub L.A., Henckel M.M., Hull S.E., Scalzo R.L., Pott G.B., Walker L.A., Reusch J.E.-B. Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease. J Hypertens. 2022 Nov 1;40(11):2133-2146. doi: 10.1097/HJH.0000000000003153. 3. Vaughan O.R., Rosario F.J., Chan J., Cox L.A., Ferchaud-Roucher V., Zemski-Berry K.A., Reusch J.E.- B., Keller A.C., Powell T.L., Jansson T. Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice. J Physiol. 2022 Jul;600(13):3169-3191. doi: 10.1113/JP282462. 4. Chun J.H., Henckel M.M., Knaub L.A., Hull S.E., Pott G., Walker, L.A., Reusch J.E.B., Keller A.C. (–)-Epicatechin improves vasoreactivity and mitochondrial respiration in thermoneutral-housed Wistar rat vasculature. Nutrients. 2022 14(5), 1097;doi.org/10.3390/nu14051097. 5. Keller, A.C., Hull, S.E., Elajaili, H., Johnston, A., Knaub, L.A., Chun, J.H., Walker, L.A., Nozik-Grayck, E., Reusch, J.E.-B. (–)-Epicatechin Modulates Mitochondrial Redox in Vascular Cell Models of Oxidative Stress. Oxidative Medicine and Cellular Longevity. 2020. doi.org/10.1155/2020/6392629 ID: 595
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Temporal analysis of mitochondrial complexome profiling coupled to multi-omics analysis unveils implications of CIV remodelling in postnatal heart development University of Cologne, Germany Bibliography
1. Porter Jr G., et al. (2011) Bioenergetics, mitochondria, and cardiac myocyte differentiation. Prog. Pediatr. Cardiol. 31, 75–81. doi: 10.1016/j.ppedcard.2011.02.002; 2. Gan J., Sonntag H-J., Tang Mk., Cai D., Lee KKH. (2015) Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome. PLoS ONE 10 (7): e0133288. doi:10.1371/journal.pone.0133288 3. Gu Y., et al. (2022) Multi-omics profiling visualizes dynamics of cardiac development and functions, Cell Reports, Volume 41, Issue 13,111891, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2022.111891. 4.Talman V., et al. (2018). Molecular Atlas of Postnatal Mouse Heart Development. J Am Heart Assoc. 2018;7:e010378. DOI: 10.1161/JAHA.118.010378 ID: 258
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial dysfunction in immune cells leads to distinct transcriptome profile and improved immune competence in Drosophila 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Molecular Biology, Umeå University, Umeå, Sweden; 3Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, United Kingdom ID: 376
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Molecular mechanisms of extraocular muscle manifestation in mitochondrial myopathy STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland Bibliography
Forsström, S., Jackson, C. B., Carroll, C. J., Kuronen, M., Pirinen, E., Pradhan, S., … Suomalainen, A. (2019). Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions. Cell Metabolism, 1–15. https://doi.org/10.1016/j.cmet.2019.08.019. Khan, N. A., Nikkanen, J., Yatsuga, S., Jackson, C., Wang, L., Pradhan, S., … Suomalainen, A. (2017). mTORC1 Regulates Mitochondrial Integrated Stress Response and Mitochondrial Myopathy Progression. Cell Metabolism, 26(2), 419-428.e5. https://doi.org/10.1016/j.cmet.2017.07.007 Pradhan, S...Lopus M (2017) “Elucidation of the Tubulin-Targeted Mechanism of Action of 9-(3-Pyridyl) Noscapine.” Cur. Top. in Medicinal Chemistry, vol. 17, no. 22, 2017, pp. 2569–74, doi:http://dx.doi.org/10.2174/1568026617666170104150304. ID: 572
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Redox metabolites and transporters: Differential expression and ratios in specific Ndufs4 knockout mice organs. Human Metabolomics, North-West University, South Africa ID: 475
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity What makes folding of a mitochondrial protein dependent on the HSP60/HSP10 chaperone complex? Aarhus University and Aarhus University Hospital, Denmark Bibliography
1.Henriques, B. J., Katrine Jentoft Olsen, R., Gomes, C. M., andBross, P. (2021) Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease Gene 145407 10.1016/j.gene.2021.145407 2.Cömert, C., Brick, L., Ang, D., Palmfeldt, J., Meaney, B. F., Kozenko, M. et al. (2020) A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy Cold Spring Harb Mol Case Stud 6, 10.1101/mcs.a004879 3.Bie, A. S., Comert, C., Korner, R., Corydon, T. J., Palmfeldt, J., Hipp, M. S. et al. (2020) An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space Cell Stress Chaperones 25, 407-416 10.1007/s12192-020-01080-6 4.Palmfeldt, J., andBross, P. (2017) Proteomics of human mitochondria Mitochondrion 33, 2-14 10.1016/j.mito.2016.07.006 ID: 385
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity OXPHOS composition is altered in the FXNI151F mouse model of Friedreich Ataxia in a progressive and a tissue-specific way Dept. Ciències Mèdiques Bàsiques, Fac. Medicina, Universitat de Lleida. IRB Lleida. Bibliography
Medina-Carbonero M, Sanz-Alcázar A, Britti E, Delaspre F, Cabiscol E, Ros J, Tamarit J. Mice harboring the FXN I151F pathological point mutation present decreased frataxin levels, a Friedreich ataxia-like phenotype, and mitochondrial alterations. Cell Mol Life Sci. 2022 Jan 17;79(2):74. ID: 482
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Disease causing-Mfn2 mutations alter mitochondrial fusion and fission dynamics and metabolism. 1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK.; 2School of Biological Sciences, Department of Cellular and Molecular Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile. ID: 284
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Dissecting the mitochondrial disease-associated ATAD3 gene cluster and its pathogenic variants 1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria,Australia; 2Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; 3Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; 4Ian Holmes Imaging Centre, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia; 5Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Victoria, Australia; 6Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia; 7Harry Perkins Institute of Medical Research and The University of Western Australia Centre for Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia; 8ARC Centre of Excellence in Synthetic Biology, QEII Medical Centre and University of Western Australia, Nedlands, Western Australia, Australia; 9Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, Australia; 10Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia ID: 340
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Dynamics of adenine nucleotides in colorectal cancer clinical material 1National Institute of Chemical Physics and Biophysics, Estonia; 2Tallinn University of Technology, Estonia; 3North Estonia Medical Centre Bibliography
Klepinin, A., Miller, S., Reile, I., Puurand, M., Rebane-Klemm, E., Klepinina, L., Vija, H., Zhang, S., Terzic, A., Dzeja, P., & Kaambre, T. (2022). Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells. Frontiers in oncology, 12, 892195. https://doi.org/10.3389/fonc.2022.892195 Reinsalu, L., Puurand, M., Chekulayev, V., Miller, S., Shevchuk, I., Tepp, K., Rebane-Klemm, E., Timohhina, N., Terasmaa, A., & Kaambre, T. (2021). Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis. Frontiers in oncology, 11, 698951. https://doi.org/10.3389/fonc.2021.698951 Kaup, K. K., Toom, L., Truu, L., Miller, S., Puurand, M., Tepp, K., Käämbre, T., & Reile, I. (2021). A line-broadening free real-time 31P pure shift NMR method for phosphometabolomic analysis. The Analyst, 146(18), 5502–5507. https://doi.org/10.1039/d1an01198g ID: 521
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The role of SURF1 protein in cytochrome c oxidase biogenesis 1Institute of Physiology of the Czech Academy of Sciences, Czech Republic; 2Institute of Microbiology, Czech Academy of Sciences, Trebon, Czech Republic; 3Departement of Biomedical Sciences, University of Padova, Padova, Italy; 4Departement of Neurosciences, University of Padova, Padova, Italy Bibliography
N. Kovářová, P. Pecina, H. Nůsková, M. Vrbacký, M. Zeviani, T. Mráček, C. Viscomi, J. Houštěk, Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects, BBA, 1862 (2016), 705-15. ID: 447
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Depicting inclusion body myositis using a patient-derived fibroblast model 1Laboratory of Inherited Metabolic Disorders and Muscle Disease, Centre de Recerca Biomèdica CELLEX - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 2Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain; 3CIBERER— Spanish Biomedical Research Centre in Rare Diseases, Madrid, Spain; 4CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; 5Universitat Pompeu Fabra (UPF), Barcelona, Spain; 6Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu; Esplugues de Llobregat, Barcelona, Spain; 7Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB-CSIC), Liver Unit-HCB-IDIBAPS, Barcelona, Spain; 8CIBEREHD-Spanish Biomedical Research Centre in Hepatic and Digestive Diseases, Madrid, Spain; 9Department of Biomedicine, Cell Biology Unit, CELLEX-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain ID: 223
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Effect of physiological cell culture media on cell viability and NRF2 activation National Institute of Chemical and Biological Physics, Estonia ID: 637
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Genetic and functional characterization of a new patient with COX4I1 deficiency 1Hospital Clinic, IDIBAPS, CIBERER, Barcelona, Spain; 2Hospital Universitario de Cruces, Spain ID: 233
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Application of the Escherichia coli Model System to Study the Human Polyribonucleotide Phosphorylase Università degli Studi di Milano, Italy ID: 523
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Phase two biotransformation is highly affected by mitochondrial disease: considerations for pharmacological therapies. Human Metabolomics, North-West University, South Africa Bibliography
1.Kühn, S., Williams, M. E., Dercksen, M., Sass, J. O., & van der Sluis, R. (2023). The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA-an in-silico and in vitro validation. Computational and Structural Biotechnology Journal, 21, 1236-1248. https://doi.org/10.1016/j.csbj.2023.01.041 2.Gruosso, F., Montano, V., Simoncini, C., Siciliano, G., & Mancuso, M. (2020). Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020. Journal of Clinical Medicine, 10(1), 94. MDPI AG. Retrieved from http://dx.doi.org/10.3390/jcm10010094 3.Fouché, B. R. (2021). Differential expression of genes involved in phase two biotransformation in an NDUFS4 deficient mouse model (Master’s dissertation, North-West University (South Africa)). http://hdl.handle.net/10394/38596 ID: 436
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial phenotyping of fibroblasts from Kearns Sayre’s patients to model the disease 1Laboratory of Inherited Metabolic Disorders and Muscle Disease, Centre de Recerca Biomèdica CELLEX - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Sciences - Universitat de Barcelona (UB); Barcelona, Spain.; 2Internal Medicine Department - Hospital Clínic de Barcelona; Barcelona, Spain.; 3CIBERER—Spanish Biomedical Research Centre in Rare Diseases; Madrid, Spain.; 4Hospital Sant Joan de Déu (HSJdD) de Barcelona, Barcelona, Spain.; 5Grupo de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (imas12). Madrid. Spain.; 6Centro de Biología Molecular S.O., Universidad Autónoma de Madrid (UAM); Madrid, Spain. ID: 343
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Effect of various mutations in the GTPase and middle domain of Drp1 on the mitochondrial network, nucleoids, and peroxisomes 1Department of Paediatrics and Inherited Metabolic Disorders, Charles University and General University Hospital in Prague, Prague, Czech Republic; 2Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic ID: 317
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Importance of human ClpXP protease for mitochondrial function First Faculty of Medicine, Charles University; and General University Hospital in Prague ID: 581
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Ketogenic diet mitigates the pathogenic phenotype in TMEM70 deficient animal models 1Institute of Physiology of the Czech Acad. Sci., Prague, Czech Republic; 2Institute of Molecular Genetics of the Czech Acad. Sci., Prague, Czech Republic; 3Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic ID: 276
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mutation in Coq5 leads to CoQ10 deficiency, developmental delay and early death in zebrafish 1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs.Granada, Granada, Spain Bibliography
[1] Malicdan MCV, Vilboux T, Ben-Zeev B, et al. A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency. Hum Mutat. 2018;39(1):69-79 ID: 364
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Omega-3 supplementation effects on mitochondrial and metabolic profile in a rabbit model of intrauterine growth restriction 1Inherited metabolic diseases and muscular disorders Lab, Cellex - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science - University of Barcelona (UB), 08036 Barcelona, Spain; 2Internal Medicine Unit, Medicine Department, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; 3Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; 4BCNatal—Barcelona Centre for Maternal-Foetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), IDIBAPS, University of Barcelona, 08036 Barcelona, Spain; 5Department of Clinical Biochemistry, Institut de Recerca de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain ID: 616
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Redundant and divergent roles of COQ8A and COQ8B in cell metabolism. 1Clinical Genetics Unit, Department of Women and Children’s Health, University of Padova and “Fondazione Istituto di Ricerca Pediatrica Città Della Speranza”, 35127 Padova, Italy.; 2Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70121 Bari, Italy; 3Department of Biomedical and Neuromotor Sciences, University of Bologna, I-40126 Bologna, Italy. ID: 305
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Loss of CHCHD8 (COA4) caused mitochondrial respiratory Complex IV deficiency National Defense Academy, Japan ID: 341
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Delving into the phenotypic heterogeneity of Coenzyme Q biosynthesis defects 1Centro Andaluz de Biología del Desarrollo/Universidad Pablo de Olavide-CSIC-JA, Seville, Spain; 2CIBERER, Instituto de Salud Carlos III, Madrid, Spain; 3Laboratorio de Fisiopatología Celular y Bioenergética, Seville, Spain. ID: 654
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Investigating the impact of mtDNA point mutations on mitochondrial function and bioenergetics using patient fibroblasts and hiPSC derived neuronal models University College London, United Kingdom ID: 632
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Human COQ10A and COQ10B genes are essential for Coenzyme Q function in mitochondrial respiration 1University of Padova, Italy; 2Isituto di Ricerca Pediatrica - Cittá della Speranza, Italy; 3Pablo de Olavide University, Sevilla, Spain Bibliography
[1] Stefely JA, Pagliarini DJ. Biochemistry of Mitochondrial Coenzyme Q Biosynthesis. Trends Biochem Sci. 2017 Oct;42(10):824-843. doi: 10.1016/j.tibs.2017.06.008. Epub 2017 Sep 17. PMID: 28927698; PMCID: PMC5731490. [2] Tsui HS, Pham NVB, Amer BR, Bradley MC, Gosschalk JE, Gallagher-Jones M, Ibarra H, Clubb RT, Blaby-Haas CE, Clarke CF. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. J Lipid Res. 2019 Jul;60(7):1293-1310. doi: 10.1194/jlr.M093534. Epub 2019 May 2. PMID: 31048406; PMCID: PMC6602128. ID: 286
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The use of β-RA in leptin-deficient mice reveals novel mechanisms of this compound for the treatment of obesity 1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs.Granada, Granada, Spain Bibliography
Santos AL, Sinha S. Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Res Rev. 2021;67:101268 Hidalgo-Gutiérrez A, Barriocanal-Casado E, Díaz-Casado ME, et al. β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight. Biomedicines. 2021;9(10):1457 ID: 274
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Oocyte-specific mitofusin 2 knockout enhances the metabolic disfunction of offspring born to obese mothers Federal University of Sao Carlos, Brazil Bibliography
GARCIA, B.M.; MACHADO, T.S.; CARVALHO, K.F.; NOLASCO, P.; NOCITI, R.P.; DEL COLLADO, M.; CAPO BIANCO, M.J.D.; GREJO, M.P.; AUGUSTO NETO, J.D.; SUGIYAMA, F.H.C.; TOSTES, K.; PANDEY, A.K.; GONÇALVES, L.M.; PERECIN, F.; MEIRELLES, F.V.; FERRAZ, J.B.S.; VANZELA, E.C.; BOSCHERO, A.C.; GUIMARÃES, F.E.G.; ABDULKADER, F.; LAURINDO, F.R. M.; KOWALTOWSKI, A.J.; CHIARATTI, M.R. Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis. Molecular Human Reproduction, v. 26, p. 938-952, 2020. ID: 489
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Off-target effects of etomoxir: inhibition of mitochondrial Complex I and fatty acid oxidation 1Oroboros Instruments, Innsbruck, Austria; 2Dept Biochem, Semmelweis Univ, Budapest, Hungary; 3CNC-Center Neurosci and Cell Biol, Univ Coimbra, Portugal; 4IIUC-Inst Interdisciplinary Research, Univ Coimbra, Portugal; 5CIBB-Center for Innovative Biomed Biotechnol, Univ Coimbra, Portugal; 6PDBEB-PhD Programme in Exp Biol Biomed, IIUC, Univ Coimbra, Portugal; 7Lab Pharmaceut Pharmacol, Latvian Inst Organic Synthesis, Riga, Latvia Bibliography
Fischer C, Valente de Souza L, Komlódi T, Garcia-Souza LF, Volani C, Tymoszuk P, Demetz E, Seifert M, Auer K, Hilbe R, Brigo N, Petzer V, Asshoff M, Gnaiger E, Weiss G (2022) Mitochondrial respiration in response to iron deficiency anemia. Comparison of peripheral blood mononuclear cells and liver. https://doi.org/10.3390/metabo12030270 Komlódi T, Tretter L (2022) The protonmotive force – not merely membrane potential. Bioenerg Commun 2022.16. https://doi.org/10.26124/bec:2022-0016 Pallag G, Nazarian S, Ravasz D, Bui D, Komlódi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited. https://doi.org/10.3390/ijms23095111 Komlódi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. https://doi.org/10.26124/bec:2021-0003 Komlódi T, Sobotka O, Gnaiger E (2021) Facts and artefacts on the oxygen dependence of hydrogen peroxide production using Amplex UltraRed. https://doi.org/10.26124/bec:2021-0004 ID: 542
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Mitochondrial alterations in sirtuin1 heterozygous mice fed high fat diet and melatonin 1Dept Biomedical Sciences for Health, University of Milan, Milan, Italy; 2Laboratorio Morfologia Umana Applicata, IRCCS Policlinico San Donato, Milan, Italy; 3Dept Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 4Center for Electron Microscopy, University of Belgrade, Belgrade, Serbia; 5Instituto de Investigaciones Biomedicas “Alberto Sols” (CSIC-UAM), Madrid, Spain Bibliography
1. Paramesha B. et al. Antioxidants (2021) 10: 338; 2. Stacchiotti A. et al. Cells (2019) 8: 1053. 3. Stacchiotti A et al. Nutrients (2017) 9:1323. ID: 1300
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Microproteins in metabolic regulation 1Duke-NUS Medical School, Singapore; 2University of Melbourne, Australia; 3University of Utah, USA; 4University of Southampton, UK Bibliography
Lena Ho, PhD (lead PI), is regarded as a pioneer in the field of microprotein research with over 30 primary research articles (5991 citations, H-index of 21) in top-tier journals. With more than 12 years of experience in microprotein discovery, functionalization and therapeutic development, Lena and her team have developed a framework of bioinformatic tools for mining ribo-seq data for disease-relevant small ORF peptides, as well as an extensive range of biochemical tools to validate their function and uncover their molecular mechanism. Lena is an EMBO Young Investigator and HHMI international scholar. Recent publications : 1) Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity. Lee CQE, Kerouanton B, Chothani S, Zhang S, Chen Y, Mantri CK, Hock DH, Lim R, Nadkarni R, Huynh VT, Lim D, Chew WL, Zhong FL, Stroud DA, Schafer S, Tergaonkar V, St John AL, Rackham OJL, Ho L. Nat Commun. 2021 Apr 9;12(1):2130. doi: 10.1038/s41467-021-22397-5. 2) Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis. Liang C, Zhang S, Robinson D, Ploeg MV, Wilson R, Nah J, Taylor D, Beh S, Lim R, Sun L, Muoio DM, Stroud DA, Ho L. Cell Rep. 2022 Aug 16;40(7):111204. doi: 10.1016/j.celrep.2022.111204. 3) Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly. Zhang S, Reljić B, Liang C, Kerouanton B, Francisco JC, Peh JH, Mary C, Jagannathan NS, Olexiouk V, Tang C, Fidelito G, Nama S, Cheng RK, Wee CL, Wang LC, Duek Roggli P, Sampath P, Lane L, Petretto E, Sobota RM, Jesuthasan S, Tucker-Kellogg L, Reversade B, Menschaert G, Sun L, Stroud DA, Ho L. 4) Viral proteases activate the CARD8 inflammasome in the human cardiovascular system. Nadkarni R, Chu WC, Lee CQE, Mohamud Y, Yap L, Toh GA, Beh S, Lim R, Fan YM, Zhang YL, Robinson K, Tryggvason K, Luo H, Zhong F, Ho L. J Exp Med. 2022 Oct 3;219(10):e20212117. doi: 10.1084/jem.20212117. Epub 2022 Sep 21. ID: 1301
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Oxphos deficiency indicates novel functions for the mitochondrial protein import subunit tim50 1Department of Biochemistry and Pharmacology and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia; 2Queensland Children’s Hospital, Department of Metabolic Medicine, South Brisbane, Brisbane, Queensland, 4001, Australia; 3Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia; 4Department of Paediatrics, University of Melbourne, Melbourne, Victoria, 3052, Australia; 5Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia ID: 1226
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The levels and activation state of the pyruvate dehydrogenase complex modulate the SCAFI-dependent organization of the mitochondrial respiratory chain 1Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain; 2Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid, Spain Bibliography
Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C. Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. 2022 Nov 1;34(11):1792-1808.e6. doi: 10.1016/j.cmet.2022.09.005. PMID: 36198313. ID: 631
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity Development of a yeast model to characterize OPA1 mutations associated with different neuromuscular disorders 1Clinical Genetics Unit, Department of Women’s and Children’s Health, University of Padua, and Istituto di Ricerca Pediatrica (IRP) Città della Speranza, Padua, Italy; 2Department of Biomedical Sciences, University of Padua, Padua, Italy ID: 263
Clinical 1: from new genes to old and novel phenotypes An ultra-special family with an ultra-rare condition: three children with mithochondrial complex III deficiency due to homozygous mutations in Lyrm7 Bolzano Hospital, Italy Bibliography
Invernizzi, Federica et al. “A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity.” Human mutation. 2013. Sánchez E et al. LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial Complex III assembly in human cells. Biochim Biophys Acta. 2013. Dallabona C. et al. LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance. Brain. 2016. Hempel M. et al. LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study. Mitochondrion. 2017. Cherian A. et al. Multifocal cavitating leukodystrophy-A distinct image in mitochondrial LYRM7 mutations. Mult Scler Relat Disord. 2021. Peruzzo R et al. Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction. Nat Commun. 2021. |
| Date: Tuesday, 13/June/2023 | |
| 8:00am - 6:30pm | Slides Center Location: Slides Center |
| 8:00am - 6:30pm | Registration Desk Location: Bologna Congress Center |
| 9:00am - 10:45am | Session 3.1: Inflammation and Immunity as mitochondrial contributor to pathology Location: Bologna Congress Center - Sala Europa Session Chair: Jose Antonio Enriquez Session Chair: Daria Diodato Invited Speakers:
S. Pluchino; M. Mittelbrunn |
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Invited
ID: 162 Invited Speakers Fuels and drivers of smouldering brain disease University of Cambridge, United Kingdom Bibliography
1. MA Leone, et al., S Pluchino, L Peruzzotti-Jametti, AL Vescovi. Foetal Allogeneic Intracerebroventricular Neural Stem Cell Transplantation in People with Secondary Progressive Multiple Sclerosis: A phase I dose-escalation clinical trial. medRxiv https://doi.org/10.1101/2022.11.14.22282124; 2. R Hamel, et al., and S Pluchino. Time-resolved single-cell RNAseq profiling identifies a novel Fabp5-expressing subpopulation of inflammatory myeloid cells in chronic spinal cord injury. bioRxiv, doi.org/10.1101/2020.10.21.346635; 3. A Mottahedin, et al., S Pluchino, L Peruzzotti-Jametti, R Goodwin, C Frezza, M Murphy and T Krieg. Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke. Redox Biology 2023; 59: 102600; 4. Peruzzotti-Jametti, et al., and S Pluchino. Neural stem cells traffic functional mitochondria via extracellular vesicles. PLoS Biol 2021, https://doi.org/10.1371/journal.pbio.3001166; 5. G Krzak, CM Willis, JA Smith, S Pluchino and L Peruzzotti-Jametti. Succinate receptor SUCNR1 (GPR91) - an emerging regulator of myeloid cell function in neuroinflammation. Trends Immunol 2021; 42(1): 45-58; 6 Pluchino S, Smith JA, Peruzzotti-Jametti L. Promises and Limitations of Neural Stem Cell Therapies for Progressive Multiple Sclerosis. Trends Mol Med 2020 Oct;26(10):898-912; 7. S Pluchino and JA Smith. Explicating Exosomes: reclassifying the rising stars in intercellular communication. Cell 2019 Apr 4;177(2):225-227; 8. L Peruzzotti-Jametti and S Pluchino. Targeting mitochondrial metabolism in neuroinflammation: towards a therapy for progressive multiple sclerosis? Trends Mol Med. 2018 Oct;24(10):838-855; 9. L Peruzzotti-Jametti, et al., and S Pluchino. Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation. Cell Stem Cell 2018 Mar 1; 22(3): 355-368; 10. N Iraci, et al., and S Pluchino. Extracellular vesicles are independent metabolic units delivering functional Asparaginase-like protein 1. Nat Chem Biol 2017 Sep;13(9):951-955. Invited
ID: 673 Invited Speakers Immunometabolisms at the crossroad between inflammation and aging CSIC- Consejo Superior de Investigaciones Cientificas, Spain Bibliography
Biology Center “Severo Ochoa” (Madrid, Spain) since 2017. Her research goal is to identify new strategies to target immune cells for boosting systemic resilience to inflammaging, cellular senescence and age-related multimorbidity. She has obtained funding from the major European and Spanish funding organizations, including an European Research Council Starting Grant in 2016, and Consolidator Grant in 2022. Among the more important discoveries from her lab: 1.Demonstration that mimicking age-associated mitochondrial dysfunction in T cells does not only recapitulate immunosenescence, but causes a general, body-wide deterioration of health with multiple aging-related features. These results place the metabolism of T cells at the crossroad between inflammation, senescence and aging, highlighting that immunometabolism can be a therapeutic target to delay aging. 2.Decoding the molecular mechanisms by which aged T cells contribute to inflammaging and age-related diseases 3.The above studies in her laboratory have allowed them to propose new therapeutic targets to delay age-related multimorbidity and to reverse aortic aneurysms and prevent sudden death due to aortic dissections Her international leadership in the field is endorsed by having been an "Invited Speaker" at more than 60 conferences and international congresses in the last 5 years, including Gordon Conferences, Cold Spring Harbor Conferences, EMBO workshops, Keystone Symposium, and participating as a keynote speaker on several occasions. She has been awarded with ,L’Oréal UNESCO for Women in Science (2015), and BANCO SABADELL AWARD for Biomedical Research (2022), Royal Spanish Acadamy of Science for Female Scientist among others. Oral presentation
ID: 491 Inflammation and Immunity as mitochondrial contributor to pathology Dissecting the role of type I interferon signaling in microglial response in a mouse model of mitochondrial disease 1Institute of Neurosciences, Autonomous University of Barcelona, Barcelona, Spain; 2Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain; 3Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pública de Navarra (UPNA), Pamplona, Spain; 4Centro de Análisis Genómico, CNAG-CRG, Barcelona, Spain Bibliography
Gella, A., Prada, P., Carrascal, M., Urpí, A., González-Torres, M., Abian, J., Sanz, E., & Quintana, A. (2020). Mitochondrial Proteome of Affected Glutamatergic Neurons in a Mouse Model of Leigh Syndrome. Frontiers in Cell and Developmental Biology, 8, 660. Oral presentation
ID: 323 Inflammation and Immunity as mitochondrial contributor to pathology The contribution of cell free-mitochondrial DNA in the pathogenesis of MELAS syndrome 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Italy; 2Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy Oral presentation
ID: 182 Inflammation and Immunity as mitochondrial contributor to pathology A novel role for the mitochondrial topoisomerase TOP1MT in mediating mtDNA release and cGAS-STING activation 1University of Calgary, Canada; 2National Institutes of Health; 3Texas A&M University; 4University of British Columbia Bibliography
Al Khatib I, Deng J, Symes SA, Zhang H, Huang S, Pommier Y, Khan A, Gibson W, Shutt TE. Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT. https://www.biorxiv.org/content/10.1101/2022.03.08.483326v1 Al Khatib I, Kerr M, Zhang H, Huang S, Pommier Y, Khan A, Shutt TE. Functional characterization of two variants in the mitochondrial topoisomerase gene TOP1MT that impact regulation of the mitochondrial genome. Journal of Biological Chemistry. 2022 Oct; 298(10):102420. Flash Talk
ID: 209 Inflammation and Immunity as mitochondrial contributor to pathology Impaired inflammatory response to lipopolysaccharide in fibroblasts from patients with long-chain fatty acid oxidation disorders 1Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 2Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 3Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark; 4Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 5Core Facility Metabolomics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands Bibliography
Mosegaard S*, Dipace G*, Bross P, Carlsen J, Gregersen N, Olsen RKJ. 2020. ”Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism”. International Journal of Molecular Sciences;21(11):3847. doi: 10.3390/ijms21113847. Mosegaard S*, Bruun GH*, Flyvbjerg KF, Bliksrud YT, Gregersen N, Dembic M, Annexstad E, Tangeraas T, Olsen RKJ, Andresen BS. 2017. “An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency”. Molecular Genetics and Metabolism;122(4):182-188. doi: 10.1016/j.ymgme.2017.10.014. Olsen RKJ*, Koňaříková E*, Giancaspero TA*, Mosegaard S*, Boczonadi V*, Mataković L*, ….. Barile M, Prokisch H. 2016. ”Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency”. American Journal of Human Genetics;98(6):1130-1145. doi: 10.1016/j.ajhg.2016.04.006. V.A. Yépez, M. Gusic, R. Kopajtich, C. Mertes, N.H. Smith, C.L. Alston, R. Ban, S. Beblo, R. Berutti, H. Blessing, E. Ciara, F. Distelmaier, P. Freisinger, J. Häberle, S.J. Hayflick, M. Hempel, Y.S. Itkis, Y. Kishita, T. Klopstock, T.D. Krylova, C. Lamperti, D. Lenz, C. Makowski, S. Mosegaard, M.F. Müller, G. Muñoz-Pujol, A. Nadel, A. Ohtake, Y. Okazaki, E. Procopio, T. Schwarzmayr, J. Smet, C. Staufner, S.L. Stenton, T.M. Strom, C. Terrile, F. Tort, R. Van Coster, A. Vanlander, M. Wagner, M. Xu, F. Fang, D. Ghezzi, J.A. Mayr, D. Piekutowska-Abramczuk, A. Ribes, A. Rötig, R.W. Taylor, S.B. Wortmann, K. Murayama, T. Meitinger, J. Gagneur, H. Prokisch, Clinical implementation of RNA sequencing for Mendelian disease diagnostics, Genome Med. 14 (2022) 38. https://doi.org/10.1186/s13073-022-01019-9. Fogh S, Dipace G, Bie A, Veiga-da-Cunha M, Hansen J, Kjeldsen M, Mosegaard S, Ribes A, Gregersen N, Aagaard L, Van Schaftingen E, Olsen RKJ. “Variants in the ethylmalonyl-CoA decarboxylase (ECHDC1) gene: a novel player in ethylmalonic aciduria?” J Inherit Metab Dis. 2021 Sep;44(5):1215-1225. doi: 10.1002/jimd.12394. Muru K., Reinson K., Künnapas K., Lilleväli H., Nochi Z., Mosegaard S., Pajusalu S., Olsen R. and Õunap K. “FLAD1 Asso-ciated Multiple Acyl-CoA Dehydrogenase Deficiency Identified by Newborn Screening.”. Molecular Genetics & Genomic Medicine;7(9). doi: 10.1002/mgg3.915. García-Villoria J., de Azua B., Tort F., Mosegaard S., Matalonga L., Ugarteburu O., Teixidó L., Olsen R. and Ribes A. “FLAD1, a recently described gene associated to multiple acyl-CoA dehydrogenase deficiency (MADD) is mutated in a patient with myopathy, scoliosis and cataracts.”. Clinical Genetics;94(6):592-593. doi: 10.1111/cge.13452. Auranen M., Paetau A., Piirilä P., Pohju A., Salmi T., Lamminen A., Thure H., Löfberg M., Mosegaard S., Olsen R., Tyni T. “FLAD1 gene mutation causes riboflavin responsive MADD disease”. Neuromuscular Disorders;27(6):581-584. doi: 10.1016/j.nmd.2017.03.003. Flash Talk
ID: 409 Inflammation and Immunity as mitochondrial contributor to pathology Fumarate induces mtDNA release via mitochondrial-derived vesicles and drives innate immunity 1Medical Research Council, MBU,University of Cambridge, UK; 2Medical Research Council Cancer Unit,University of Cambridge, UK; 3CECAD Research Centre, University of Cologne, Cologne, Germany Bibliography
AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology. Tilokani L, Russell FM, Hamilton S, Virga DM, Segawa M, Paupe V, Gruszczyk AV, Protasoni M, Tabara LC, Johnson M, Anand H, Murphy MP, Hardie DG, Polleux F, Prudent J. Sci Adv. 2022 Nov 11;8(45):eabo7956. doi: 10.1126/sciadv.abo7956. Epub 2022 Nov 11. PMID: 36367943 Mitochondrial translation is required for sustained killing by cytotoxic T cells. Lisci M, Barton PR, Randzavola LO, Ma CY, Marchingo JM, Cantrell DA, Paupe V, Prudent J, Stinchcombe JC, Griffiths GM. Science. 2021 Oct 15;374(6565):eabe9977. doi: 10.1126/science.abe9977. Epub 2021 Oct 15. PMID: 34648346 Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division. Nagashima S, Tábara LC, Tilokani L, Paupe V, Anand H, Pogson JH, Zunino R, McBride HM, Prudent J. Science. 2020 Mar 20;367(6484):1366-1371. doi: 10.1126/science.aax6089. PMID: 32193326 SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA. EMBO Mol Med. 2016 Sep 1;8(9):1019-38. doi: 10.15252/emmm.201506159. Print 2016 Sep. PMID: 27390132 CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter. Paupe V, Prudent J, Dassa EP, Rendon OZ, Shoubridge EA. Cell Metab. 2015 Jan 6;21(1):109-16. doi: 10.1016/j.cmet.2014.12.004. PMID: 25565209 Flash Talk
ID: 430 Inflammation and Immunity as mitochondrial contributor to pathology Free cytosolic-mitochondrial DNA triggers a potent type-I Interferon response in Kearns–Sayre patients counteracted by mofetil mycophenolate 1Unit of Cellular Biology and Diagnosis of Mitochondrial Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; 2Division of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Division of Metabolism, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Research Unit of Muscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy |
| 10:45am - 11:00am | Coffee Break Location: Bologna Congress Center |
| 11:00am - 12:40pm | Session 3.2: Mitochondrial mechanisms in neurodegeneration and neurodevelopment Location: Bologna Congress Center - Sala Europa Session Chair: Vincent Procaccio Session Chair: Elena Rugarli Invited Speaker: V. Paquis-Flucklinger; L. Burbulla |
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Invited
ID: 675 Invited Speakers Destructuring of mitochondrial cristae in the initiation of CHCHD10-related neurodegeneration 1IRCAN, UMR 7284/INSERM U1081/UCA, Nice, France; 2Reference Center for mitochondrial diseases, Universitary hospital, Nice, France Invited
ID: 670 Invited Speakers Convergence of mitochondrial and lysosomal dysfunction in Parkinson’s disease Ludwig Maximilian University (LMU) Munich, Germany Oral presentation
ID: 588 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Development of cortical organoids to model m.3243A>G disease and understand cell specificity University of Cambridge, United Kingdom Oral presentation
ID: 623 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Brain and brainstem-specific mitochondrial diversity associated with vulnerability to neurodegeneration in mitochondrial diseases 1Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York NY, USA; 2Center for Translational & Computational Neuroimmunology, Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, New York NY, USA; 3Division of Molecular Therapeutics, Department of Psychiatry, Columbia University Irving Medical Center, New York NY, USA; 4Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; 5Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; 6New York State Psychiatric Institute, New York NY, USA; 7Department of Neurology, Columbia University Irving Medical Center, New York NY, USA Oral presentation
ID: 527 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial DNA mutations exacerbate motor and behavioural deficits in a mouse model of Parkinson’s disease 1Clinical and Translational Research Institute, Centre for Life, Newcastle University, UK, NE3 1BZ; 2Department of Clinical Neuroscience, University of Cambridge, UK, CB2 0QQ; 3Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK, CB2 0QQ; 4Division of Molecular Metabolism, Biomedicum, floor 9D, Solnavägen 9, Karlolinska Institute, 171 65 Stockholm, Sweden; 5Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, NE4 5PL Bibliography
Nie, Yu, et al. "Heteroplasmic mitochondrial DNA mutations in frontotemporal lobar degeneration." Acta Neuropathologica 143.6 (2022): 687-695. Murley, Alexander G., et al. "High-Depth PRNP Sequencing in Brains With Sporadic Creutzfeldt-Jakob Disease." Neurology Genetics 9.1 (2023). Burr, Stephen P., et al. "Cell lineage-specific mitochondrial resilience during mammalian organogenesis." Cell (2023). Flash Talk
ID: 556 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Macromolecular crowding: A novel player in mitochondrial physiology and disease 1Radboud University Medical Center, The Netherlands; 2University of Amsterdam, The Netherlands; 3King's College, London, UK; 4University of Twente, The Netherlands; 5Wageningen University, The Netherlands Bibliography
Bulthuis EP, Dieteren CEJ, Bergmans J, Berkhout J, Wagenaars JA, van de Westerlo EMA, Podhumljak E, Hink MA, Hesp LFB, Rosa HS, Malik AN, Lindert MK, Willems PHGM, Gardeniers HJGE, den Otter WK, Adjobo-Hermans MJW, Koopman WJH. Stress-dependent macromolecular crowding in the mitochondrial matrix. EMBO J. 2023 Feb 24:e108533. doi: 10.15252/embj.2021108533. Epub ahead of print. PMID: 36825437. Bulthuis EP, Adjobo-Hermans MJW, Willems PHGM, Koopman WJH. Mitochondrial Morphofunction in Mammalian Cells. Antioxid Redox Signal. 2019 Jun 20;30(18):2066-2109. doi: 10.1089/ars.2018.7534. Epub 2018 Nov 29. Dieteren CE, Gielen SC, Nijtmans LG, Smeitink JA, Swarts HG, Brock R, Willems PH, Koopman WJ. Solute diffusion is hindered in the mitochondrial matrix. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8657-62. doi: 10.1073/pnas.1017581108. Epub 2011 May 9. PMID: 21555543; PMCID: PMC3102363. Flash Talk
ID: 342 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Preserved motor function and striatal innervation despite severe degeneration of dopamine neurons upon mitochondrial dysfunction 1Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne, Germany; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK; 3Medical Research Council Mitochondrial Biology Unit and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, UK; 4Department of Neurology, Faculty of Medicine and University Hospital Cologne, Germany; 5Institute of Radiochemistry and Experiment Molecular Imaging, Faculty of Medicine and University Hospital of Cologne, Germany; 6Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine and University Hospital Cologne, Germany; 7Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Center for Molecular Medicine Cologne, University of Cologne, Germany Bibliography
(1) Ricke, K.M., T. Paß, S. Kimoloi, K. Fährmann, C. Jüngst, A. Schauss, O.R. Baris, M. Aradjanski, A. Trifunovic, T.M. Eriksson Faelker, M. Bergami and R.J. Wiesner (2020): Mitochondrial dysfunction combined with high calcium load leads to impaired antioxidant defense underlying the selective loss of nigral dopaminergic neurons. J Neuroscience 40: 1975-1986 (2) Dölle C., Flønes I., Nido G.S., Miletic H., Osuagwu N., Kristoffersen S., Lilleng P.K., Larsen J.P., Tysnes O.B., Haugarvoll K., Bindoff L.A., Tzoulis C. (2016): Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun. 7: 13548. Flash Talk
ID: 320 Mitochondrial mechanisms in neurodegeneration and neurodevelopment The mitochondrial DNA depletion syndrome protein FBXL4 mediates the degradation of the mitophagy receptors BNIP3 and NIX to suppress mitophagy 1School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia; 2Department of Biotechnology, School of Biotechnology, Viet Nam National University-International University, Ho Chi Minh City, Vietnam; 3Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, USA; 4Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, USA; 5The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia; 6Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 8The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia Bibliography
Nguyen-Dien G, Kozul K, Cui Y, Townsend B, Gosavi Kulkarni P, Ooi S, Marzio A, Carrodus N, Zuryn S, Pagano M et al. (2022) FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. bioRxiv 2022.10.12.511867; doi: https://doi.org/10.1101/2022.10.12.511867 |
| 12:40pm - 12:45pm | Conference Picture Location: Bologna Congress Center - Sala Europa |
| 12:45pm - 1:15pm | Industry Workshop: Oroboros Location: Bologna Congress Center - Sala Europa |
| 12:45pm - 1:45pm | Lunch Location: Bologna Congress Center - Sala Europa |
| 1:45pm - 3:30pm | Session 3.3: Metabolic stress responses in mitochondrial diseases and cancer Location: Bologna Congress Center - Sala Europa Session Chair: Luca Scorrano Session Chair: Luisa Iommarini Invited Speaker: A. Trifunovic; L. Greaves |
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Invited
ID: 195 Metabolic stress responses in mitochondrial diseases, ageing and cancer Transcriptional regulation of mitochondrial stress responses University of Cologne, Germany Bibliography
1.Croon M, Szczepanowska K, Popovic M, Lienkamp C, Senft K, Brandscheid CP, Theresa Bock T, Gnatzy-Feik L, Ashurov A, Acton RA, Kaul H, Pujol C, Rosenkranz S, Krüger M and Trifunovic A. (2022) FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction. Sci Adv. 2022 Apr 8;8(14):eabn7105. 2.Rumyantseva A, Popovic M and Trifunovic A. (2022) CLPP deficiency ameliorates neurodegeneration caused by impaired mitochondrial protein synthesis. Brain Feb 11;e109169. 3.Kaspar, S., Oertlin, C., Szczepanowska, K., Kukat, A., Senft, K., Lucas, C., Brodesser, S., Hatzoglou, M., Larsson, O., Topisirovic, I., Trifunovic, A. (2021) Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR. Sci. Adv. 7, eabf0971 Invited
ID: 678 Invited Speakers Mitochondrial DNA mutations in ageing and cancer - what's the connection? 1Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; 2MRC Mitochondrial Biology Unit, Cambridge, United Kingdom; 3CRUK Beatson Institute, Glasgow, United Kingdom Bibliography
Gorelick, A. N., M. Kim, W. K. Chatila, K. La, A. A. Hakimi, M. F. Berger, B. S. Taylor, P. A. Gammage and E. Reznik (2021). "Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA." Nat Metab 3(4): 558-570. Greaves, L. C., M. J. Barron, S. Plusa, T. B. Kirkwood, J. C. Mathers, R. W. Taylor and D. M. Turnbull (2010). "Defects in multiple complexes of the respiratory chain are present in ageing human colonic crypts." Exp Gerontol 45(7-8): 573-579. Smith, A. L. M., J. C. Whitehall, C. Bradshaw, D. Gay, F. Robertson, A. P. Blain, G. Hudson, A. Pyle, D. Houghton, M. J. Hunt, J. N. Sampson, C. Stamp, G. Mallett, S. Amarnath, J. Leslie, F. Oakley, L. Wilson, A. Baker, O. M. Russell, R. Johnson, C. A. Richardson, B. Gupta, I. McCallum, S. A. C. McDonald, S. Kelly, J. C. Mathers, R. Heer, R. W. Taylor, N. D. Perkins, D. M. Turnbull, O. J. Sansom and L. C. Greaves (2020). "Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis." Nature Cancer 1(10): 976-989. Oral presentation
ID: 452 Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria 1Folkhälsan Research Center, Finland; 2Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Finland; 3Viikki Metabolomics Unit, University of Helsinki, Finland; 4Division of Infection Medicine, Department of Clinical Sciences, Lund University, Sweden; 5Colzyx AB, Lund, Sweden; 6Department of Clinical Sciences, Lund, Pediatrics, Lund University, Sweden; 7Children’s Hospital, Helsinki University Hospital, Finland Bibliography
Purhonen J., Banerjee R, Wanne V. Sipari N. Mörgelin M. Fellman V. and Kallijärvi J. Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria. BioRxiv 2023; 01.10.521980. Purhonen J. and Kallijärvi J. Quantification of all 12 canonical ribonucleotides by real-time fluorogenic in vitro transcription. BioRxiv 2023; 02.18.527797. Banerjee R. Purhonen J. and Kallijärvi, J. The mitochondrial coenzyme Q junction and complex III: biochemistry and pathophysiology. The FEBS Journal 2021; 289, 6936–6958. Purhonen J, Banerjee R, McDonald AE, Fellman V, Kallijärvi J. A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye, and inhibitor-resistant high-fidelity DNA polymerase. Nucleic Acids Research 2020: gkaa516 Purhonen J, Grigorjev V, Ekiert R, Aho N, Rajendran J, Wikström M, Sharma V, Osyczka A, Fellman V, Kallijärvi J. A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice. Nature Communications 2020;11:1–12. Rajendran J, Purhonen J, Tegelberg S, Smolander OP, Mörgelin M, Rozman J, Gailus-Durner J, Fuchs H, Hrabe de Angelis M, Auvinen P, Mervaala E, Jacobs HT, Szibor M, Fellman V, Kallijärvi J. Alternative oxidase‐mediated respiration prevents lethal mitochondrial cardiomyopathy. EMBO Molecular Medicine 2019;11:e9456. Oral presentation
ID: 624 Metabolic stress responses in mitochondrial diseases, ageing and cancer A genetic deficiency screen in vivo reveals rescue mechanisms of mitochondrial dysfunction 1Karolinska Institutet, Sweden; 2Max-Planck Institute of Biochemistry, Germany; 3University of Cambridge, Cambridge Biomedical Campus, UK Oral presentation
ID: 456 Metabolic stress responses in mitochondrial diseases, ageing and cancer Heterochromatin Protein 1 controls gene expression and longevity in response to mitochondrial dysfunction 1Andalusian Centre for Developmental Biology (CABD). CSIC-Universidad Pablo de Olavide-Junta de Andalucía. Carretera de Utrera Km 1, 41013 Sevilla, Spain.; 2Department of Molecular Biology and Biochemical Engineering, Universidad Pablo de Olavide. Carretera de Utrera Km 1, 41013 Seville, Spain; 3Department of Biochemistry, Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. Flash Talk
ID: 381 Metabolic stress responses in mitochondrial diseases, ageing and cancer High fat diet ameliorates the mitochondrial cardiomyopathy of CHCHD10 mutant mice Weill Cornell Medicine, United States of America Flash Talk
ID: 413 Metabolic stress responses in mitochondrial diseases, ageing and cancer Functional characterisation of the human mitochondrial disaggregase, CLPB 1Department of Biochemistry and Pharmacology, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville VIC 3010, Australia; 2Murdoch Children’s Research Institute, Royal Children’s Hospital and Department of Paediatrics, The University of Melbourne, Parkville VIC 3052, Australia; 3Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Parkville VIC 3052, Australia Flash Talk
ID: 448 Metabolic stress responses in mitochondrial diseases, ageing and cancer The mitochondrial inhibitor IF1 has a dual role in cancer 1Department of Biomedical and Neuromotor Sciences, University of Bologna; 2Department of Chemical Science, University of Padova; 3Department of Biology, University of Padova, Padova Bibliography
1. Galber, C; Fabbian, S; Gatto, C; Grandi, M; Carissimi, S; Acosta, MJ; Sgarbi, G; Tiso, N; Argenton, F; Solaini, G; Baracca, A; Bellanda, M; Giorgio,CELL DEATH & DISEASE, 2023, 14, pp. 1 - 19 2. Gatto, C; Grandi, M; Solaini, G; Baracca, A; Giorgio, V, FRONTIERS IN PHYSIOLOGY, 2022, 13, 917203, pp. 1 - 11 3. Galber C; Minervini G; Cannino G; Boldrin F; Petronilli V; Tosatto S; Lippe G; Giorgio V, CELL REPORTS, 2021, 35, 109111, pp. 1 - 14 |
| 3:30pm - 3:50pm | Industry Workshop: UCB Farchim SA Location: Bologna Congress Center - Sala Europa |
| 3:30pm - 4:30pm | Tea Break and poster session Location: Bologna Congress Center Session topics: - Clinical 2: natural history, biomarkers and outcome measures - Inflammation and Immunity as mitochondrial contributor to pathology - Metabolic stress responses in mitochondrial diseases, ageing and cancer |
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ID: 653
Clinical 2: natural history, biomarkers and outcome measures Evaluating functional mobility and endurance in adults with Primary Mitochondrial Myopathy (PMM); insights concerning gait protocol and outcome measure selection. 1Translational and Clinical Research Institute, Newcastle University, UK; 2National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; 3Newcastle Clinical Trials Unit, Newcastle University, UK; 4Population Health Sciences Institute, Newcastle University, UK; 5Pharmacy Directorate, The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; 6The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; 7Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, UK; 8NHS Highly Specialised Service for Rare Mitochondrial Disorders, The Newcastle upon Tyne Hospitals NHS Foundation Trust, UK ID: 173
Clinical 2: natural history, biomarkers and outcome measures Natural variability in protein expression of oxidative deficiency markers in single muscle fibres and tissue homogenate mitochondrial genetics in m.3243A>G-related myopathy 1Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne, United Kingdom; 3Centre for Doctoral Training in Cloud Computing and Big Data, Newcastle upon Tyne, United Kingdom Bibliography
Bernardino Gomes, T. (2019). The best care for children with facioscapulohumeral dystrophy. Dev Med Child Neurol, 61(8), 865. doi:10.1111/dmcn.14158 Bernardino Gomes, T. M., Ng, Y. S., Pickett, S. J., Turnbull, D. M., & Vincent, A. E. (2021). Mitochondrial DNA disorders: From pathogenic variants to preventing transmission. Hum Mol Genet. doi:10.1093/hmg/ddab156 Horrigan, J., Gomes, T. B., Snape, M., Nikolenko, N., McMorn, A., Evans, S., . . . Lochmuller, H. (2020). A Phase 2 Study of AMO-02 (Tideglusib) in Congenital and Childhood-Onset Myotonic Dystrophy Type 1 (DM1). Pediatric Neurology, 112, 84-93. doi:10.1016/j.pediatrneurol.2020.08.001 Leo, V. D., Lawless, C., Roussel, M.-P., Gomes, T. B., Gorman, G. S., Russell, O. M., . . . Vincent, A. E. (2023). Strength training rescues mitochondrial dysfunction in skeletal muscle of patients with myotonic dystrophy type 1. medRxiv, 2023.2001.2020.23284552. doi:10.1101/2023.01.20.23284552 ID: 402
Clinical 2: natural history, biomarkers and outcome measures Retrospective natural history of mitochondrial deoxyguanosine kinase deficiency: a worldwide cohort of 197 patients 1Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna; 2IRCCS Istituto delle Scienze Neurologiche, Neuropsichiatria dell’età pediatrica, Bologna; 3Department of Biochemistry, Bicêtre Hospital, Reference Center for Mitochondrial Disease, University of Paris-Saclay, Assistance Publique-Hôpitaux de Paris, France; 4School of Medicine, Institute of Human Genetics, Technical University of Munich,Germany; 5Institute of Neurogenomics, Computational Health Center, Helmholtz Zentrum München, Neuherberg, Germany; 6H. Houston Merritt Neuromuscular Research Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; 7Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 8Pediatric Hepatology and Pediatric Liver Transplantation Unit, Bicêtre Hospital, Reference Center for Mitochondrial Disease, University of Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Paris, France; 9Center for Medical Genetics, Department of Metabolism, Chiba Children's Hospital, 579-1 Heta-cho, Midori-ku, Chiba, 266-000, Japan; 10Diagnostics and Therapeutic of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan; 11Department of Pediatrics, University Hospital Centre Zagreb, Zagreb, Croatia; 12Clinic for Pediatrics, Division of Inherited Metabolic Disorders, Medical University of Innsbruck, 6020 Innsbruck, Austria; 13University Children's Hospital, Paracelsus Medical University (PMU), 5020 Salzburg, Austria; 14Division of Metabolism, Bambino Gesù Children's Hospital IRCCS, Rome, Italy; 15Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 16IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 17Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.; 18Dipartimento Di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.; 19Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany; 20MitoLab, UMR CNRS 6015 - INSERM U1083, MitoVasc Institute , Angers University Hospital, Angers, France; 21Centre de référence des maladies héréditaires du métabolisme, CHU la Timone Enfants, Marseille, France; 22Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Regional Clinical Center for expanded newborn screening, Milan, Italy; 23Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy.; 24Unité de Gastroentérologie, Hépatologie, Nutrition et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Toulouse, France; 25Division of Medical Genetics and Neurogenetics, Fondazione IRCCS Neurological Institute "C. Besta", Milan, Italy; 26Division of Neuropaediatrics and Paediatric Metabolic Medicine, Center for Paediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany; 27Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa & AOUP, Italy; 28Unit of Neurology and Neuromuscular Disorders, Department of Clinical and experimental Medicine, University of Messina, Italy; 29Department of Paediatrics, Medical Sciences Division, Oxford University, Oxford OX3 9DU, UK; 30Metabolic Unit, Meyer Children's Hospital IRCCS, Florence, Italy; 31Centre de référence des Maladies Mitochondriales, Service de Génétique Médicale, CHU de Nice, Université Côte d’Azur, CNRS, INSERM, IRCAN, Nice, France; 32Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; 33Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel ID: 315
Clinical 2: natural history, biomarkers and outcome measures Tissue, molecular and metabolic changes in the liver of patients with Mitochondrial Neurogastrointestinal Encephalomyopathy 1Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna. Italy; 3Department of Life Quality Studies (QuVI), University of Bologna, Bologna, Italy; 4University Hospital Vall d'Hebron. Barcelona. Spain; 5IRCCS St. Orsola. Bologna. Italy; 6Department of Translational Medicine, University of Ferrara, Ferrara, Italy Bibliography
1. Hirano M et al. and Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mi-tochondrial disorder. Neurology 44: 721–727, 1994. doi:10.1212/wnl.44.4.721 2. Hirano M et al Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE In-ternational Network. J Inherit Metab Dis 1–12, 2020. doi:10.1002/jimd.12300. 3. De Giorgio R et al. Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Ann Neurol 80: 448–455, 2016. doi:10.1002/ana.24724 ID: 206
Clinical 2: natural history, biomarkers and outcome measures Phenotyping mtDNA-related diseases in childhood: a cohort study of 150 patients Fondazione IRCCS Besta, Milan Italy Bibliography
Please enter recent publications by the first author. 1. Mitochondrial epilepsy: a cross-sectional nationwide Italian survey. Ticci C, Sicca F, Ardissone A, Bertini E, Carelli V, Diodato D, Di Vito L, Filosto M, La Morgia C, Lamperti C, Martinelli D, Moroni I, Musumeci O, Orsucci D, Pancheri E, Peverelli L, Primiano G, Rubegni A, Servidei S, Siciliano G, Simoncini C, Tonin P, Toscano A, Mancuso M, Santorelli FM. Neurogenetics. 2020 Apr;21(2):87-96 2.ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy. Caporali L, Magri S, Legati A, Del Dotto V, Tagliavini F, Balistreri F, Nasca A, La Morgia C, Carbonelli M, Valentino ML, Lamantea E, Baratta S, Schöls L, Schüle R, Barboni P, Cascavilla ML, Maresca A, Capristo M, Ardissone A, Pareyson D, Cammarata G, Melzi L, Zeviani M, Peverelli L, Lamperti C, Marzoli SB, Fang M, Synofzik M, Ghezzi D, Carelli V, Taroni F. Ann Neurol. 2020 Jul;88(1):18-32 3. A homozygous MRPL24 mutation causes a complex movement disorder and affects the mitoribosome assembly. Di Nottia M, Marchese M, Verrigni D, Mutti CD, Torraco A, Oliva R, Fernandez-Vizarra E, Morani F, Trani G, Rizza T, Ghezzi D, Ardissone A, Nesti C, Vasco G, Zeviani M, Minczuk M, Bertini E, Santorelli FM, Carrozzo R. Neurobiol Dis. 2020 Jul;141:104880 4.Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I. Alahmad A, Nasca A, Heidler J, Thompson K, Oláhová M, Legati A, Lamantea E, Meisterknecht J, Spagnolo M, He L, Alameer S, Hakami F, Almehdar A, Ardissone A, Alston CL, McFarland R, Wittig I, Ghezzi D, Taylor RW. EMBO Mol Med. 2020 Nov 6;12(11) 5.SARS-CoV-2 infection in patients with primary mitochondrial diseases: features and outcomes in Italy. Mancuso M, La Morgia C, Lucia Valentino M, Ardissone A, Lamperti C, Procopio E, Garone C, Siciliano G, Musumeci O, Toscano A, Primiano G, Servidei S, Carelli V. Mitochondrion. 2021 May;58:243-245 6.Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases. Ticci C, Orsucci D, Ardissone A, Bello L, Bertini E, Bonato I, Bruno C, Carelli V, Diodato D, Doccini S, Donati MA, Dosi C, Filosto M, Fiorillo C, La Morgia C, Lamperti C, Marchet S, Martinelli D, Minetti C, Moggio M, Mongini TE, Montano V, Moroni I, Musumeci O, Pancheri E, Pegoraro E, Primiano G, Procopio E, Rubegni A, Scalise R, Sciacco M, Servidei S, Siciliano G, Simoncini C, Tolomeo D, Tonin P, Toscano A, Tubili F, Mancuso M, Battini R, Santorelli FM. J Clin Med. 2021 May 12;10(10):2063 7.Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases. Ardissone A, Bruno C, Diodato D, Donati A, Ghezzi D, Lamantea E, Lamperti C, Mancuso M, Martinelli D, Primiano G, Procopio E, Rubegni A, Santorelli F, Schiaffino MC, Servidei S, Tubili F, Bertini E, Moroni I. Orphanet J Rare Dis. 2021 Oct 9;16(1):413 8. Kearns-Sayre syndrome: expanding spectrum of a "novel" mitochondrial leukomyeloencephalopathy. Moscatelli M, Ardissone A (co-first author), Lamantea E, Zorzi G, Bruno C, Moroni I, Erbetta A, Chiapparini L. Neurol Sci. 2022 Mar;43(3):2081-2084 ID: 262
Clinical 2: natural history, biomarkers and outcome measures Carrier frequency of pathogenic and likely pathogenic variants in POLG in Eastern Norway 1Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; 2Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; 3Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway; 4Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway; 5Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway; 6Metabolic Unit, Great Ormond Street Hospital, London, UK.; 7Mitochondrial Research Group, Genetics and Genomic Medicine Department, UCL Great Ormond Street Institute of Child Health, London, UK.; 8Department of Neurology, Haukeland University Hospital, Bergen, Norway; 9Nasjonal kompetansetjeneste for medfødte stoffskiftesykdommer, Oslo University Hospital, Oslo, Norway; 10Department of Pediatrics, Haukeland University Hospital, Bergen, Norway ID: 470
Clinical 2: natural history, biomarkers and outcome measures Exercise testing and measurement of habitual physical activities in m.3243A>G-related Mitochondrial Disease 1Wellcome Centre for Mitochondrial Research. Clinical and Translational Research Institute. Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle upon Tyne Hospitals NHS Foundation Trust Bibliography
Cassidy S, Trenell M, Stefanetti RJ, Charman SJ, Barnes AC, Brosnahan N, McCombie L, Thom G, Peters C, Zhyzhneuskaya S, Leslie WS. Physical activity, inactivity and sleep during the Diabetes Remission Clinical Trial (DiRECT). Diabetic Medicine. 2022 Nov 18:e15010. Abouhajar A, Alcock L, Bigirumurame T, Bradley P, Brown L, Campbell I, Del Din S, Faitg J, Falkous G, Gorman GS, Lakey R. Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy. Trials. 2022 Dec;23(1):1-5. Stefanetti RJ, Ng YS, Errington L, Blain AP, McFarland R, Gorman GS. L-arginine in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes: a systematic review. Neurology. 2022 Jun 7;98(23):e2318-28. Houghton D, Ng YS, Jackson MA, Stefanetti R, Hynd P, Mac Aogáin M, Stewart CJ, Lamb CA, Bright A, Feeney C, Newman J. Phase II Feasibility Study of the Efficacy, Tolerability, and Impact on the Gut Microbiome of a Low-Residue (Fiber) Diet in Adult Patients With Mitochondrial Disease. Gastro Hep Advances. 2022 Jan 1;1(4):666-77 ID: 568
Clinical 2: natural history, biomarkers and outcome measures Leber’s hereditary optic neuropathy in females. 1Dipartimento di Scienze Biomediche e Neuromotorie, University of Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 3IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Bologna, Italy Bibliography
1.Carelli V, D'Adamo P, Valentino ML, La Morgia C, Ross-Cisneros FN, Caporali L, Maresca A, Loguercio Polosa P, Barboni P, De Negri A, Sadun F, Karanjia R, Salomao SR, Berezovsky A, Chicani F, Moraes M, Moraes Filho M, Belfort Jr R, Sadun AA. Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion. Brain. 2016. mar; 139, e17. 2.Lopez Sanchez MIG, Kearns LS, Staffieri SE, Clarke L, McGuinness MB, Meteoukki W, Samuel S, Ruddle JB, Chen C, Fraser CL, Harrison J, Hewitt AW, Howell N, Mackey DA. Establishing risk of vision loss in Leber hereditary optic neuropathy. Am J Hum Genet. 2021 Nov 4;108(11):2159-2170. doi: 10.1016/j.ajhg.2021.09.015. Epub 2021 Oct 19. PMID: 34670133; PMCID: PMC8595929. ID: 539
Clinical 2: natural history, biomarkers and outcome measures Non-invasive tool for mitochondrial diseases diagnostics 1Laboratory of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic; 21st Faculty of medicine, Charles University, Prague, Czech Republic ID: 333
Clinical 2: natural history, biomarkers and outcome measures Obstetric history of women with m.3243A>G – a retrospective cohort study University of Oulu and Oulu University Hospital, Finland Bibliography
n/a ID: 429
Clinical 2: natural history, biomarkers and outcome measures Clustering analysis with optical coherence tomography data in Leber hereditary optic neuropathy (LHON) patients by non-negative matrix factorization unsupervised learning technique 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica - Bologna (Italy); 2Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna - Bologna (Italy); 3IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica - Bologna (Italy); 4Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele – Milan (Italy); 5Studio Oculistico d’Azeglio - Bologna (Italy) Bibliography
Yu-Wai-Man P, Votruba M, Burte F, La Morgia C, Barboni P, Carelli V. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathol. 2016 Dec;132(6):789-806. Barboni P, Savini G, Valentino ML, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology. 2005 Jan;112(1):120-6. Balducci N, Savini G, Cascavilla ML, et al. Macular nerve fibre and ganglion cell layer changes in acute Leber's hereditary optic neuropathy. Br J Ophthalmol. 2016 Sep;100(9):1232-7. Barboni P, Savini G, Feuer WJ, et al. Retinal nerve fiber layer thickness variability in Leber hereditary optic neuropathy carriers. Eur J Ophthalmol. 2012 Nov-Dec;22(6):985-91. Gaujoux R, Seoighe C. A flexible R package for nonnegative matrix factorization. BMC Bioinformatics. 2010 Jul 2;11:367. ID: 135
Clinical 2: natural history, biomarkers and outcome measures Leigh syndrome global patient registry - cure mito foundation 1Cure Mito Foundation, United States of America; 2Cure Mito Foundation, United States of America; 3Cure Mito Foundation, United States of America; Johns Hopkins University School of Medicine; 4Cure Mito Foundation, United States of America; 5Cure Mito Foundation, United States of America; 6Perot Foundation Neuroscience Transla-tional Research Center (PNTRC), The University of Texas Southwestern Medical Center O'Donnell Brain Institute; 7Midwestern University College of Pharmacy; 8Midwestern University College of Pharmacy; 9Cure Mito Foundation; The University of Texas Southwestern Medical Center ID: 552
Clinical 2: natural history, biomarkers and outcome measures Mitochondrial ATP synthase deficiency and its relationship with the urea cycle 1Division of Metabolism, Department of Pediatric Subspecialties, Bambino Gesù Children's Hospital, Rome, Italy; 2Laboratory of Metabolic Diseases, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy; 3Unit of Muscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy Bibliography
1.Dvorakova V, Magner M, Honzik T. Hyperammonemic crisis in a child with ATP synthase deficiency caused by mtDNA mutation m.8851T>C. Mol Genet Metab Rep. 2014;2:46. Published 2014 Dec 18. 2.Žigman T, Šikić K, Petković Ramadža D, et al. ATP synthase deficiency due to m.8528T>C mutation - a novel cause of severe neonatal hyperammonemia requiring hemodialysis. J Pediatr Endocrinol Metab. 2020;34(3):389-393. Published 2020 Nov 13. 3.Magner M, Dvorakova V, Tesarova M, et al. TMEM70 deficiency: long-term outcome of 48 patients [published correction appears in J Inherit Metab Dis. 2015 May;38(3):583-4. Morava-Kozicz, Eva [corrected to Morava, Eva]]. J Inherit Metab Dis. 2015;38(3):417-426. 4.Honzík T, Tesarová M, Mayr JA, et al. Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation. Arch Dis Child. 2010;95(4):296-301. 5. Staretz-Chacham O, Wormser O, Manor E, Birk OS, Ferreira CR. TMEM70 deficiency: Novel mutation and hypercitrullinemia during metabolic decompensation. Am J Med Genet A. 2019;179(7):1293-1298. ID: 289
Clinical 2: natural history, biomarkers and outcome measures Quantifying ataxia in adult patients with primary mitochondrial disease 1Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; 2NIHR Newcastle Biomedical Research Centre, Newcastle University; 3NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 4Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK ID: 407
Clinical 2: natural history, biomarkers and outcome measures Retrospective natural history study of MTRFR/C12orf65-related disorders 1East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 2Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (add-tr.mitoteam@nhs.net); 3Hereditary Neuropathy Foundation, New York, NY, USA (https://www.hnf-cure.org/) ID: 466
Clinical 2: natural history, biomarkers and outcome measures Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibres 1Lund University, Sweden; 2A&E Department, Kungälv Hospital, Kungälv, Sweden; 3Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland; 4Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark; 5Skåne University Hospital, Department of Intensive- and perioperative Care, Malmö, Sweden; 6Department of Pediatrics, Skåne University Hospital, Lund University, Lund, Sweden; 7Clinical Physiology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden; 8Department of Pediatrics, The Queen Silvia Children’s Hospital, University of Gothenburg, Gothenburg, Sweden; 9Lund University, Department of Clinical Sciences Lund, Translational Neurology Group and Wallenberg Center for Molecular Medicine, Lund, Sweden; 10Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Otorhinolaryngology, Head and Neck Surgery, Lund, Sweden ID: 154
Clinical 2: natural history, biomarkers and outcome measures Epidemiology and the natural history of POLG disease in Norway 1Department of Medical Biochemistry, Oslo University Hospital, Norway; 2Department of Clinical Medicine (K1), University of Bergen, Norway; 3Department of Medical Genetics, Oslo University Hospital, Norway; 4Department of Medical Genetics, Haukeland University Hospital, Norway; 5Paediatric Research Group, Department of Clinical Medicine, UiT The Artic University of Norway, Norway; 6Department of Paediatrics, University Hospital of North Norway, Norway; 7Department of Neurology, St. Olav’s Hospital, University Hospital, Norway; 8Department of Neuroscience and Movement Science, Faculty of Medicine, Norwegian University of Science and Technology, Norway; 9Unit for Congenital and Hereditary Neuromuscular Conditions (EMAN), Department of Neurology, Oslo University Hospital, Norway; 10Department of Clinical Neurosciences for Children, Oslo University Hospital, Norway; 11Norwegian National Unit for Newborn Screening, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway. European Reference Network for Hereditary Metabolic Disorders; 12Metabolic Unit, Great Ormond Street Hospital, London, UK. European Reference Network for Hereditary Metabolic Disorders; 13Mitochondrial Research Group, Genetics and Genomic Medicine Department, UCL Great Ormond Street Institute of Child Health, UK; 14Department of Neurology, Haukeland University Hospital, Norway; 15Department of Pediatrics, Haukeland University Hospital, Norway Bibliography
1.Bendiksen Skogvold H, Yazdani M, Sandås EM, Østeby Vassli A, Kristensen E, Haarr D, et al. A pioneer study on human 3-nitropropionic acid intoxication: Contributions from metabolomics. J Appl Toxicol. 2022;42(5):818-29. 2.Böhm HO, Yazdani M, Sandås EM, Østeby Vassli A, Kristensen E, Rootwelt H, et al. Global Metabolomics Discovers Two Novel Biomarkers in Pyridoxine-Dependent Epilepsy Caused by ALDH7A1 Deficiency. Int J Mol Sci. 2022;23(24). 3.Tangeraas T, Ljungblad UW, Lutvica E, Kristensen E, Rowe AD, Bjørke-Monsen AL, et al. Vitamin B12 Deficiency (Un-)Detected Using Newborn Screening in Norway. Int J Neonatal Screen. 2023;9(1). 4.Jamali A, Kristensen E, Tangeraas T, Arntsen V, Sikiric A, Kupliauskiene G, et al. The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study. Epilepsy Research. 2023;190:107099. ID: 529
Clinical 2: natural history, biomarkers and outcome measures The evolving phenotypic profile of cardiomyopathy in patients with Barth syndrome 1Medical University of South Carolina, Charleston, SC, United States of America; 2Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America; 3Henry Ford Hospital, Detroit, MI, United States of America; 4Stealth BioTherapeutics, Inc, Needham, MA, United States of America ID: 251
Clinical 2: natural history, biomarkers and outcome measures True or false mitochondrial disorder? 1INSERM UMR1163, Université Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; 2Departments of Pediatric and Genetics, Hôpital Necker-Enfants-Malades, Paris, France; 3CARAMMEL reference center for mitochondrial diseases ID: 629
Clinical 2: natural history, biomarkers and outcome measures An automated processing pipeline to perform probabilistic tractography of the anterior optic pathway applied to Leber’s hereditary optic neuropathy. 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 3Department of Physics and Astronomy, University of Bologna, Bologna, Italy Bibliography
1. Manners DN, Gramegna LL, La Morgia C, Sighinolfi G, Fiscone C, Carbonelli M, Romagnoli M, Carelli V, Tonon C, Lodi R. Multishell Diffusion MR Tractography Yields Morphological and Microstructural Information of the Anterior Optic Pathway: A Proof-of-Concept Study in Patients with Leber's Hereditary Optic Neuropathy. Int J Environ Res Public Health. 2022 Jun 5;19(11):6914. doi: 10.3390/ijerph19116914 2. He J, Zhang F, Xie G, Yao S, Feng Y, Bastos DCA, Rathi Y, Makris N, Kikinis R, Golby AJ, O'Donnell LJ. Comparison of multiple tractography methods for reconstruction of the retinogeniculate visual pathway using diffusion MRI. Hum Brain Mapp. 2021 Aug 15;42(12):3887-3904. doi: 10.1002/hbm.25472 ID: 200
Clinical 2: natural history, biomarkers and outcome measures Natural history of Pearson syndrome: various clinical courses with changes in clinical phenotypes 1Department of Paediatrics and Adolescent Medicine, Division of Paediatric Haematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Germany; 2Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, University Medical Center, University of Freiburg, Freiburg, Germany; 3Department of Paediatric Oncology, Haematology and Clinical Immunology, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany; 4Department of Paediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany; 5Medical University of Innsbruck, Clinic for Paediatrics, Inherited Metabolic Disorders, Innsbruck, Austria Bibliography
, ID: 494
Clinical 2: natural history, biomarkers and outcome measures Phenotype and natural history of pantothenate kinase-associated neurodegeneration (PKAN) 1Department of Neurology With Friedrich Baur Institute, University Hospital of Ludwig-Maximilians-Universität München, Munich, Germany; 2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 3Munich Cluster for Systems Neurology, Munich, Germany ID: 575
Clinical 2: natural history, biomarkers and outcome measures RARS2 disease’s morbidity and mortality correlate with the severity of brain involvement 1Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Neuropsichiatria dell’età pediatrica, Bologna, Italy; 3Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum University of Bologna, Bologna, Italy; 4IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy ID: 172
Clinical 2: natural history, biomarkers and outcome measures A new non-invasive diagnostic method for detection of pathogenic mitochondrial DNA variants using faecal-derived DNA samples. 1Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute; NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; 2Department of Neurosciences, NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne NE2 4HH, UK ID: 235
Clinical 2: natural history, biomarkers and outcome measures Complex V assembly intermediates in human muscle from patient with suspected mitochondrial disease - Potential insights into disease mechanisms. 1Neurometabolic Unit, NHNN, University College London Hospitals; 2Chemical Pathology Laboratory, Great Ormond Street Hospital for Children; 3Queen Square Institute of Neurology, University College London; 4Great Ormond Street Institute of Child Health, University College London Bibliography
Poole OV, et al., 2019 Adult-onset Leigh syndrome linked to the novel stop codon mutation m.6579G>A in MT-CO1. Mitochondrion. 2019 Jul;47:294-297. Bugiardini E et al., 2020 Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations. Neurol Genet. 2020 Jan 7;6(1):e381. Keshavan N., (2020) The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency. Genet Med. 2020 Jan;22(1):199-209. Forny P et al., 2021 Diagnosing Mitochondrial Disorders Remains Challenging in the Omics Era. Neurol Genet. 2021 May 25;7(3):e597. Schober FA, et al., 2022 Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease. Hum Mol Genet. 2022 Jun 22;31(12):2049-2062. Kaiyrzhanov R et al., 2022 Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement. Am J Hum Genet. 2022 Sep 1;109(9):1692-1712. ID: 219
Clinical 2: natural history, biomarkers and outcome measures Prolonged gastrointestinal transit times in mitochondrial disease – a case control study 1Dept. of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; 2Dept.of Clinical Medicine, Aalborg University, Aalborg, Denmark; 3Mech-Sense, Dept. of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark; 4Dept. of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark Bibliography
Bone Deformities and Kidney Failure: Coincidence of PHEX-Related Hypophosphatemic Rickets and m.3243A>G Mitochondrial Disease. Nielsen SR, Hansen SG, Bistrup C, Brusgaard K, Frederiksen AL. Calcif Tissue Int.2022 Dec;111(6):641-645 FGF21 and glycemic control in patients with T1D. Rosell Rask S, Krarup Hansen T, Bjerre M. Endocrine 2019 Aug 65(3): 550-557 ID: 129
Clinical 2: natural history, biomarkers and outcome measures Rethinking mitochondrial diabetes: a multifaceted disease entity 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3Endocrinology Department, University College London Hospital, London, UK ID: 583
Clinical 2: natural history, biomarkers and outcome measures Therapeutic intervention in Leber Hereditary Optic Neuropathy: later is better? 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica - Bologna (Italy); 2Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna - Bologna (Italy); 3IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica - Bologna (Italy); 4Department ofOphthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele – Milan (Italy); 5Studio Oculistico d’Azeglio - Bologna (Italy) Bibliography
Subramanian PS, Newman NJ, Moster M, et al. Study design and baseline characteristics for the REFLECT gene therapy trial of m.11778G>A/ND4-LHON. BMJ Open Ophthalmology 2022;7:e001158. doi:10.1136/bmjophth-2022-001158. Catarino CB, von Livonius B, Priglinger C, Banik R, Matloob S, Tamhankar MA, et al. Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy. J Neuroophthalmol. 2020;40(4):558-65. ID: 645
Clinical 2: natural history, biomarkers and outcome measures Neurofilament light chain – an emerging biomarker in mitochondrial disease 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.; 2Department of Biomedical and Neuromotor Sciences, University of Bologna,; 3Department of Clinical Medicine (K1), University of Bergen, Bergen, Norway; 4Dept. of Neurology, Haukeland University Hospital, Norway; 5Neuro-SysMed - Centre of Excellence for Experimental Therapy in Neurology, Departments of Neurology and Clinical Medicine, Bergen, Norway ID: 450
Inflammation and Immunity as mitochondrial contributor to pathology Assessing the role of mtdsRNA as a trigger for neuroinflammation in a mouse model of Leigh syndrome 1Institute of Neurosciences, Autonomous University of Barcelona, Barcelona, Spain; 2Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain ID: 406
Inflammation and Immunity as mitochondrial contributor to pathology Concerted cell-specific neuronal programs drive neurodegeneration in Leigh Syndrome Universitat Autònoma de Barcelona, Spain Bibliography
* Microglial response promotes neurodegeneration in the Ndufs4 KO mouse model of Leigh syndrome. Aguilar K, Comes G, Canal C, Quintana A, Sanz E, Hidalgo J. Glia. 2022 Nov;70(11):2032-2044. doi: 10.1002/glia.24234. * Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention. van de Wal MAE, Adjobo-Hermans MJW, Keijer J, Schirris TJJ, Homberg JR, Wieckowski MR, Grefte S, van Schothorst EM, van Karnebeek C, Quintana A, Koopman WJH. Brain. 2022 Mar 29;145(1):45-63. doi: 10.1093/brain/awab426. * Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within. Luna-Sánchez M, Bianchi P, Quintana A. Int J Mol Sci. 2021 Aug 7;22(16):8523. doi: 10.3390/ijms22168523. * Defined neuronal populations drive fatal phenotype in a mouse model of Leigh syndrome. Bolea I, Gella A, Sanz E, Prada-Dacasa P, Menardy F, Bard AM, Machuca-Márquez P, Eraso-Pichot A, Mòdol-Caballero G, Navarro X, Kalume F, Quintana A. Elife. 2019 Aug 12;8:e47163. doi: 10.7554/eLife.47163. * Mitochondrial Proteome of Affected Glutamatergic Neurons in a Mouse Model of Leigh Syndrome. Gella A, Prada-Dacasa P, Carrascal M, Urpi A, González-Torres M, Abian J, Sanz E, Quintana A. Front Cell Dev Biol. 2020 Jul 28;8:660. doi: 10.3389/fcell.2020.00660. eCollection 2020. ID: 526
Inflammation and Immunity as mitochondrial contributor to pathology Parkinson’s disease genes converge at the mitochondria-lysosome interface to promote inflammatory cell death McGill University, Canada Bibliography
Collier JJ, Olahova M, McWilliams TG, Taylor RW. Mitochondrial signalling and homeostasis: from cell biology to neurological disease. Trends in Neurosciences. 2023;46(2):137-152. Collier JJ, Guissart C, Olahova M, Sasorith S, Piron-Prunier F, Suomi F, Zhang D, Martinez-Lopez N, Leboucq N, Bahr A, Azzarello-Burri S, Reich S, Schols L, Polvikoski TM, Meyer P, Larrieu L, Schaefer AM, Alsaif HS, Alyamani S, Zuchner S, Barbosa IA, Deshpande C, Pyle A, Rauch A, Synofzik M, Alkuraya FS, Rivier F, Ryten M, McFarland R, Delahodde A, McWilliams TG, Koenig M, Taylor RW. Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans. New England Journal of Medicine. 2021;384(25):2406-2417. Collier JJ, Suomi F, Olahova M, McWilliams TG, Taylor RW. Emerging roles of ATG7 in human health and disease. EMBO Molecular Medicine. 2021;13(12)e14824. Thompson K*, Collier JJ*, Glasgow RIC, Robertson FM, Pyle A, Alston CL, Blakely EL, Olahova M, McFarland R, Taylor RW. Recent advances in understanding the molecular genetic basis of mitochondrial disease. Journal of Inherited Metabolic Disorders 2020;43:36-50. Review. *Co-first authors Nolden KA, Egner JM, Collier JJ, Russell OM, Alston CL, Harwig MC, Widlansky ME, Sasorith S, Barbosa IA, Douglas AG, Baptista J, Walker M, Donnelly DE, Morris AA, Tan HJ, Kurian MA,Gorman K, Mordekar S, Deshpande C, Samanta R, McFarland R, Hill RB, Taylor RW, Olahova M. Novel DNM1L variants impair mitochondrial dynamics through divergent mechanisms. Life SciAlliance. 2022;5(12). Olahova M, Peter B, Diaz H, Szilagyi Z, Sommerville EW, Blakely EL, Collier JJ, Stránecký V, Hartmannová H, Bleyer AJ, McBride KL, Bowden SA, Korandová Z, Pecinová A, Ropers H-H, Kahrizi K, Najmabadi H, Tarnopolsky M, Brady LI, Weaver N, Prada CE, Õunap K, Wojcik MH, Pajusalu S, Syeda SB, Pais L, Estrella EA, Bruels CC, Kunkel LM, Kang PB, Mráček T, Kmoch S, Gorman G, Falkenberg M, Gustafsson C, Taylor RW. Mutations in POLRMT cause a spectrum of neurological phenotypes through impaired mitochondrial transcription. Nature Communications 2021;12,1135 Olahova M, Ceccatelli Berti C, Collier JJ, Alston CL, Jameson E, Jones SA, Edwards N, He L, Chinnery PF, Horvath R, Goffrini P, Taylor RW, Sayer JA. Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease. Human Molecular Genetics 2019;28:3766-76. ID: 642
Inflammation and Immunity as mitochondrial contributor to pathology [18F]ROStrace PET as a biomarker of mitochondria-induced neuroinflammation in the prodromal phase of Parkinson’s disease mouse models 1Children's Hospital of Philadelphia, United States of America; 2University of Pennsylvania, United States of America Bibliography
1.Hsieh CJ, Hou C, Zhu Y, Lee JY, Kohli N, Gallagher E, Xu K, Lee H, Li S, McManus MJ, Mach RH. [18F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer's disease pathology in APP/PS1 mice. EJNMMI Res. 2022 Jul 27;12(1):43. ID: 651
Inflammation and Immunity as mitochondrial contributor to pathology Modulation of immune cell activation and differentiation by mitochondrial nicotinamide adenine dinucleotide levels 1Instituto Universitario de Biología Molecular – UAM (IUBM-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain; 2Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain ID: 257
Inflammation and Immunity as mitochondrial contributor to pathology MtDNA replication stress and innate immune signalling Max Planck Institute for Biology of Ageing, Germany Bibliography
Misic J, Milenkovic D. Methods Mol Biol. 2023;2615:219-228.Studying Mitochondrial Nucleic Acid Synthesis Utilizing Intact Isolated Mitochondria. Misic J, Milenkovic D, Al-Behadili A, Xie X, Jiang M, Jiang S, Filograna R, Koolmeister C, Siira SJ, Jenninger L, Filipovska A, Clausen AR, Caporali L, Valentino ML, La Morgia C, Carelli V, Nicholls TJ, Wredenberg A, Falkenberg M, Larsson NG. Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Res. 2022 Aug 26;50(15):8749-8766. Milenkovic D, Sanz-Moreno A, Calzada-Wack J, Rathkolb B, Veronica Amarie O, Gerlini R, Aguilar-Pimentel A, Misic J, Simard ML, Wolf E, Fuchs H, Gailus-Durner V, de Angelis MH, Larsson NG.Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction. PLoS Genet. 2022 May 9;18(5):e1010190. Sprenger HG, MacVicar T, Bahat A, Fiedler KU, Hermans S, Ehrentraut D, Ried K, Milenkovic D, Bonekamp N, Larsson NG, Nolte H, Giavalisco P, Langer T.Cellular pyrimidine imbalance triggers mitochondrial DNA-dependent innate immunity. Nat Metab. 2021 May;3(5):636-650. Matic S, Jiang M, Nicholls TJ, Uhler JP, Dirksen-Schwanenland C, Polosa PL, Simard ML, Li X, Atanassov I, Rackham O, Filipovska A, Stewart JB, Falkenberg M, Larsson NG, Milenkovic D.Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria. Nat Commun. 2018 Mar 23;9(1):1202. ID: 241
Inflammation and Immunity as mitochondrial contributor to pathology Inflammatory cardiomyopathy and heart failure caused by impaired inner membrane integrity 1Institut Pasteur, Mitochondrial Biology Group, CNRS UMR 3691, Université Paris Cité, Paris, France; 2Department of Translational Research, Comprehensive Heart Failure Center (CHFC), Medical Clinic 1, University ClinicWürzburg,Würzburg, Germany; 3Institut Pasteur, Biomics Technological Platform, Université Paris Cité, Paris, France; 4Institut Pasteur, Proteomics Core Facility, MSBio UtechS, UAR CNRS 2024, Université Paris Cité, Paris, France Bibliography
Donnarumma, E., Kohlhaas, M., Vimont, E., Kornobis, E., Chaze, T., Gianetto, Q.G., Matondo, M., Moya-Nilges, M., Maack, C., and Wai, T. (2022). Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure. Nat. Commun. 13, 6634. 10.1038/s41467-022-34316-3. ID: 650
Inflammation and Immunity as mitochondrial contributor to pathology Lack of SIRT3 results in a constitutive IFNbeta release and protects against viral infection 1Instituto Universitario de Biología Molecular – UAM (IUBM-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain; 2Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid (CSIC-UAM), 28049 Madrid, Spain ID: 372
Inflammation and Immunity as mitochondrial contributor to pathology Mitochondrial DNA variation alters cell-mediated and humoral innate immune responses 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, UK Bibliography
Valanne, S., Vesala, L., Maasdorp, M., Salminen T.S., and Rämet, M. 2022: The Drosophila Toll pathway in innate immunity – from the core pathway towards effector functions. J Immunol 2022; 209:1817-1825; doi: 10.4049/jimmunol.2200476 Anderson L., Camus M.F., Monteith K.M., Salminen T.S. and Vale P.F. 2022: Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster. Heredity, 129, pages 225–232 https://doi.org/10.1038/s41437-022-00554-w Salminen T.S. & Vale P.F. 2020: Drosophila as a model system to investigate the effects of mitochondrial variation on innate immunity. Front. Immunol. 11:521.doi: 10.3389/fimmu.2020.00521 Valanne S., Järvelä-Stölting M., Harjula S-K. E., Myllymäki H., Salminen T.S. & Rämet M. 2020: Osa-containing Brahma complex regulates innate immunity and metabolism in Drosophila. J. Immunol. DOI: https://doi.org/10.4049/jimmunol.1900571 Salminen T.S., Cannino G., Oliveira M.T., Lillsunde P., Jacobs H.T., Kaguni L.S. 2019: Lethal interaction of nuclear and mitochondrial genotypes in Drosophila melanogaster. G3: GENES, GENOMES, GENETICS 9 (7): 2225-2234: doi: https://doi.org/10.1534/g3.119.400315 Valanne S*., Salminen T.S.*, Järvelä-Stölting M., Vesala L. & Rämet M. 2019: Correction: Immune-inducible non-coding RNA molecule lincRNA-IBIN connects immunity and metabolism in Drosophila melanogaster. PLoS Pathog 15(1): e1007504. DOI: 10.1371/journal.ppat.1008088 *Shared first authorship Salminen T.S., Oliveira M.T., Cannino G., Lillsunde P., Jacobs H.T. & Kaguni L.S. 2017: Mitochondrial genotype modulates mtDNA copy number and organismal phenotype in Drosophila. Mitochondrion 34: 75-83. ID: 177
Inflammation and Immunity as mitochondrial contributor to pathology Iron homeostasis in mitochondria is critical for the survival of T cells University of Michigan, United States of America ID: 567
Inflammation and Immunity as mitochondrial contributor to pathology Inflammatory conditions, redox status and c-miRNAs as potential predictors of vascular damage in type 2 diabetes mellitus patients. 1Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Spain; 2Institute of Biotechnology, Biomedical Research Center, Health Sciences Technology Park, University of Granada, Granada, Spain; 3Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Investigación Biosanitaria (Ibs), Granada, San Cecilio University Hospital, Granada, Spain; 4Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Almaty, Kazakhstan; 5Departamento de Investigación y Extensión, Centro de Enseñanza Técnica Industrial; Guadalajara, Jalisco, México; 6Hospital de Alcalá la Real, Andalucia, Spain; 7Endocrinology and Nutrition Unit, Instituto de Investigación Biosanitaria de Granada (Ibs.GRANADA), University Hospital Clínico San Cecilio, Granada, Spain.; 8Department of Physiology, Faculty of Medicine, University of Granada. Bibliography
1. Acuña-Castroviejo, D.; Rahim, I.; Acuña-Fernández, C.; Fernández-Ortiz, M.; Solera-Marín, J.; Sayed, R.K.A.; Díaz-Casado, M.E.; Rusanova, I.; López, L.C.; Escames, G. Melatonin, clock genes and mitochondria in sepsis. Cell. Mol. Life Sci. 2017, 74, doi:10.1007/s00018-017-2610-1. 2. Rovira-Llopis, S.; Apostolova, N.; Bañuls, C.; Muntané, J.; Rocha, M.; Victor, V.M. Mitochondria, the NLRP3 inflammasome, and sirtuins in type 2 diabetes: New therapeutic targets. Antioxidants Redox Signal. 2018, 29, 749–791, doi:10.1089/ars.2017.7313. 3. Mensà, E.; Giuliani, A.; Matacchione, G.; Gurău, F.; Bonfigli, A.R.; Romagnoli, F.; De Luca, M.; Sabbatinelli, J.; Olivieri, F. Circulating miR-146a in healthy aging and type 2 diabetes: Age- and gender-specific trajectories. Mech. Ageing Dev. 2019, 180, 1–10, doi:10.1016/j.mad.2019.03.001. 4. Rusanova, I.; Fernández-Martínez, J.; Fernández-Ortiz, M.; Aranda-Martínez, P.; Escames, G.; García-García, F.J.; Mañas, L.; Acuña-Castroviejo, D. Involvement of plasma miRNAs, muscle miRNAs and mitochondrial miRNAs in the pathophysiology of frailty. Exp. Gerontol. 2019, 124, doi:10.1016/j.exger.2019.110637. 5. López-Armas, G. C., Yessenbekova, A., González-Castañeda, R. E., Arellano-Arteaga, K. J., Guerra-Librero, A., Ablaikhanova, N., Florido, J., Escames, G., Acuña-Castroviejo, D., & Rusanova, I. (2022 Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients. Antioxidants 2022, 11. ID: 664
Inflammation and Immunity as mitochondrial contributor to pathology Loss of pathogenic mitochondrial tRNA mutations during the development of adaptive immune responses 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden; 2Max Planck Institute Biology of Ageing-Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm 17165, Sweden.; 3Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Stockholm 17176, Sweden; 4Center for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm 17164, Sweden.; 5Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden. ID: 311
Inflammation and Immunity as mitochondrial contributor to pathology Role of mitochondrial dynamics in abdominal aortic aneurysm 1UMR CNRS 6015, INSERM U1083, MitoVasc Institute, CarMe Team, University of Angers, France; 2CHU of Angers, France ID: 261
Inflammation and Immunity as mitochondrial contributor to pathology Between benefit and harm – the effect of antibiotics-induced mitochondrial stress on innate immune responses Tampere University, Finland ID: 232
Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial thermo-profiles of diverse cell lines show reduction of thermo-stability at pathophysiological conditions 1Tampere University, Finland; 2University of Copenhagen; 3Osaka University Bibliography
Ignatenko O, Chilov D, Paetau I, de Miguel E, Jackson CB, Capin G, Paetau A, Terzioglu M, Euro L, Suomalainen A. Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy. Nat Commun. 2018 Jan 4;9(1):70. doi: 10.1038/s41467-017-01859-9. PMID: 29302033; PMCID: PMC5754366. ID: 171
Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial thermogenesis and thermal adaptation in fibroblasts 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland ID: 507
Metabolic stress responses in mitochondrial diseases, ageing and cancer Effects of SIRT1 modulators in a pregnancy-induced mouse model of primary mitochondrial cardiomyopathy 1Neuroscience Graduate Program, Will Cornell Graduate School of Medical Sciences, 1300 York Ave, New York, NY 10065, USA; 2Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY 10065, USA.; 3Elysium Health New York, New York, NY 10013, USA Bibliography
Sayles, N. M., Southwell, N., McAvoy, K., Kim, K., Pesini, A., Anderson, C. J., Quinzii, C., Cloonan, S., Kawamata, H., & Manfredi. "Mutant CHCHD10 Causes an Extensive Metabolic Rewiring That Precedes OXPHOS Dysfunction in a Murine Model of Mitochondrial Cardiomyopathy." Cell Reports, 2022, https://doi.org/10.1016/j.celrep.2022.110475. ID: 111
Metabolic stress responses in mitochondrial diseases, ageing and cancer A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance 1Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia; 2ARC Centre of Excellence in Synthetic Biology, QEII Medical Centre, Nedlands, Western Australia 6009, Australia; 3Centre for Medical Research, The University of Western Australia, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.; 4Max Planck Institute for Biology of Ageing, D-50931 Cologne, Germany; 5Faculty of Health and Medical Sciences, Medical School, The Rural Clinical School of Western Australia, The University of Western Australia, Bunbury, Western Australia 6230, Australia; 6Department of Anatomy and Embryology, Faculty of Medicine, Laboratory Animal Resource Center (LARC), and Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; 7Dobney Hypertension Centre, Medical School, The University of Western Australia, Perth, Western Australia, Australia; 8Australian National Phenome Centre, Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth, Western Australia 6150, Australia; 9School of Human Sciences (Physiology), The University of Western Australia, Crawley, Western Australia 6009, Australia.; 10Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, New South Wales 2010, Australia.; 11Curtin Medical School, Curtin University, Bentley, Western Australia 6102, Australia; 12Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia 6102, Australia.; 13Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, Australia. Bibliography
1. Vos PD, Rossetti G, Mantegna JL, Siira SJ, Gandadireja AP, Bruce M, Raven SA, Khersonsky O, Fleishman SJ, Filipovska A, Rackham O. Computationally designed hyperactive Cas9 enzymes. Nat Commun. 2022 May 31;13(1):3023. doi: 10.1038/s41467-022-30598-9. 2. Rossetti, G., Ermer, J. A., Stentenbach, M., Siira, S. J., Richman, T. R., Milenkovic, D., Perks, K. L., Hughes, L. A., Jamieson, E., Xiafukaiti, G., Ward, N. C., Takahashi, S., Gray, N., Viola, H. M., Hool, L. C., Rackham, O., & Filipovska, A. A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance. Science Advances, 7(39), (2021). [eabi7514]. https://doi.org/10.1126/sciadv.abi7514 3. Richman, T. R., Ermer, J. A., Siira, S. J., Kuznetsova, I., Brosnan, C. A., Rossetti, G., Baker, J., Perks, K. L., Cserne Szappanos, H., Viola, H. M., Gray, N., Larance, M., Hool, L. C., Zuryn, S., Rackham, O. & Filipovska, A., Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan Aging Cell (2021). 20, 7, e13408. 4. Ferreira, N., Andoniou, C. E., Perks, K.L., Ermer, J.A., Rudler, D.L., Rossetti, G., Periyakaruppiah, A., Wong, J. K. Y., Rackham, O., Noakes, P. G., Degli-Esposti, M. A., Filipovska, A. Murine cytomegalovirus infection exacerbates Complex IV deficiency in a model of mitochondrial disease. PLOS Genetics (2020) 16(3):e1008604. 5. Perks KL, Ferreira N, Ermer JA, Rudler DL, Richman TR, Rossetti G, Matthews VB, Ward NC, Rackham O, Filipovska A. Reduced mitochondrial translation prevents diet-induced metabolic dysfunction but not inflammation. EMBO J. (2019) Dec 16;38(24):e102155. doi: 10.15252/embj.2019102155. Epub 2019 Nov 13.PMID: 31721250 6. Ferreira, N, Perks, K.L., Rossetti, G., Rudler, D.L., Hughes, L., Ermer, J.A., Scott, L., Kuznetsova, I., Szappanos,H.C, Tull D., Yeoh, G.C., Hool, L.C., Filipovska, A. and Rackham, O. Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation EMBO Journal (2019) 38(24):e102155. 7. Perks, K.L., Rossetti, G., Kuznetsova, I., Hughes, L., Ermer, J.A., Ferreira, N., Rudler, D., Spahr,H., Busch, J.D., Shearwood, A.M.-J., Viola, H.M, Siira, S.J., Milenković, D., Hool, L.C., Larsson, N.-G., Rackham, O. and Filipovska, A. PTCD1 is required for 16S rRNA maturation complex stability and mitochondrial ribosome assembly. Cell Reports (2018) 23(1):127-142. 8. Siira, S.J., Rossetti, G., Richman, T.R., Perks, K.L., Ermer, J.E., Kuznetsova, I., Hughes, L., Shearwood, A.M.-J., Viola, H.M, Hool, L.C., Rackham, O. and Filipovska, A. Concerted regulation of mitochondrial and nuclear non-coding RNAs by a dual-targeted RNase Z. EMBO Reports (2018) pii: e46198. doi: 10.15252/embr.201846198 9. Butchart, L. C., Terrill, J. R., Rossetti, G., White, R., Filipovska, A., & Grounds, M. D. (2018). Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during postnatal growth of normal and dystrophic (Mdx) mouse muscles, and their response to taurine treatment. International Journal of Biochemistry and Cell Biology, 99(October 2017), 52–63. https://doi.org/10.1016/j.biocel.2018.03.016 10. Duff, R. M., Shearwood, A. M. J., Ermer, J., Rossetti, G., Gooding, R., Richman, T. R., Balasubramaniam, S., Thorburn, D.R., Rackham, O., Lamont, P.J., Filipovska, A. (2015). A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome. Mitochondrion, 25, 113–119. https://doi.org/10.1016/j.mito.2015.10.008 ID: 609
Metabolic stress responses in mitochondrial diseases, ageing and cancer Metformin enhanced the Effect of Ketogenic Diet and low Dose of Cyclophosphamide in MYCN-amplified Neuroblastoma 1Paracelsus Medical University, Austria; 2Shuzhao Li Lab The Jackson Laboratory for Genomic Medicine, Farmington, USA; 3Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute; 4Core Facilities, Medical University of Vienna, Vienna, Austria Bibliography
1.Oliynyk, G., et al., MYCN-enhanced Oxidative and Glycolytic Metabolism Reveals Vulnerabilities for Targeting Neuroblastoma. iScience, 2019. 21: 188-204. 2.Weber, D.D., et al., Ketogenic diet in the treatment of cancer - Where do we stand? Mol Metab, 2020. 33: 102-121. 3.Wheaton, W.W., et al., Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. Elife, 2014. 3: e02242. 4.Ruiz-Perez, M.V., et al., Inhibition of fatty acid synthesis induces differentiation and reduces tumor burden in childhood neuroblastoma. iScience, 2021. 24(2): 102128. ID: 293
Metabolic stress responses in mitochondrial diseases, ageing and cancer Respiratory complex I deficiency triggers integrated stress response upon metabolic challenge 1University of Bologna, Department of Pharmacy and Biotechnology, Italy; 2University of Bologna, Department of Medical and Surgical Sciences, Italy; 3University of Bologna, Department of Biomedical and Neuromotor Sciences, Italy; 4University of Padua, Department of Biomedical Sciences, Italy ID: 288
Metabolic stress responses in mitochondrial diseases, ageing and cancer Stress responses in a novel mitochondrial myopathy mouse model Bogazici University, Turkey ID: 597
Metabolic stress responses in mitochondrial diseases, ageing and cancer The multifaceted role of GDF15 in mitochondrial muscle disease and its synergistic action with FGF21 1University of Helsinki, Finland; 2Nadmed Ltd, Helsinki, Finland; 3NGM Biopharmaceuticals, South San Francisco, CA 94080, USA ID: 596
Metabolic stress responses in mitochondrial diseases, ageing and cancer Red 630 light transcranial LED therapy (RL-TCLT) stimulates bioenergetic mitochondrial function, enhancing neuronal arborization and reducing hippocampal memory loss in aged SAMP8 mice. 1Neurobiology of Aging Lab, CEBICEM, Universidad San Sebastián, Chile; 2Centro Ciencia & Vida, Fundación Ciencia & Vida, Chile.; 3Escuela de Ingeniería Civil Biomédica, Universidad de Valparaíso, Chile. ID: 357
Metabolic stress responses in mitochondrial diseases, ageing and cancer The mitokine GDF15 correlates with differentially dietary fat intake in pregnancies with intrauterine growth restriction 1Inherited metabolic diseases and muscular disorders Lab, Cellex - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science - University of Barcelona (UB), 08036 Barcelona, Spain; 2Internal Medicine Unit, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; 3Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; 4BCNatal—Barcelona Centre for Maternal-Foetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), IDIBAPS, University of Barcelona, 08036 Barcelona, Spain; 5Medicine Department, Faculty of Medicine. CIBEROBN Obesity and Nutrition Physiopathology. Institut de Recerca en Nutrició i Seguretat Alimentaria (INSA-UB). University of Barcelona, Barcelona, Spain. Fundación Dieta Mediterránea, Barcelona, Spain, ID: 179
Metabolic stress responses in mitochondrial diseases, ageing and cancer Telomerase is crucial for mitochondrial function in human cardiomyocytes 1Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany; 2REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany; 3Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany Bibliography
1.Lu D*, Chatterjee S*, Xiao K*, et al. A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. (2022) European Heart Journal. doi: 10.1093/eurheartj/ehac337 *equal contribution 2.Olliges L, Chatterjee S, Jia L, et al. Multiformin-type azaphilones prevent SARS-CoV-2 binding to ACE2 receptor. (2022) Cells. doi: 10.3390/cells12010083 3.Bei Y†, Lu D†, Bär C†, Chatterjee S, et al. MiR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection (2022) Mol. Ther. doi: 10.1016/j.ymthe.2022.01.031 †equal contribution 4.Chatterjee S*, Hofer T*, Costa A, et. al. Telomerase therapy attenuates cardiotoxic effects of doxorubicin (2020) Mol. Ther. doi: 10.1016/j.ymthe.2020.12.035 *equal contribution 5.Lu D*, Chatterjee S*, Xiao K, et al. MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes (2020) J Mol Cell Cardiol. 2020;148:46-49. doi: 10.1016/j.yjmcc.2020.08.017 *equal contribution ID: 535
Metabolic stress responses in mitochondrial diseases, ageing and cancer Drug repositioning as a mitochondrial-targeted therapeutic approach for neurodegenerations associated with OPA1 mutations 1Dept. Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 3Dept. Pharmacy and Biotechnology (FABIT), University of Bologna, Italy; 4Dept. Chemistry, Life Science and Environmental Sustainability, University of Parma, Italy ID: 602
Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondria hormesis delays aging and associated diseases in C. elegans impacting on key ferroptosis players 1Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany; 2Humboldt-Universität zu Berlin, Berlin, Germany; 3Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, Norway; 4Institute of Clinical Chemistry and Laboratory Diagnostic, Medical Faculty, Heinrich Heine University of Düsseldorf, Germany ID: 230
Metabolic stress responses in mitochondrial diseases, ageing and cancer Cross-talk between mitochondria and immunoproteasomes upon mitochondrial dysfunction IMol Polish Academy of Sciences, Warsaw, Poland ID: 585
Metabolic stress responses in mitochondrial diseases, ageing and cancer Diagnostic examination of kinase inhibitors by bioenergetic profiling of cancer cell models reveals off-target drug effects 1Division of Medical Biochemistry, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; 2Tyrolean Cancer Research Institute (TKFI), Innrain 66, 6020 Innsbruck, Austria.; 3Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; 4Oroboros Instruments, Schoepfstrasse 18, 6020 Innsbruck, Austria Bibliography
1.Cohen, P, Cross, D, Jänne, PA (2021). Kinase drug discovery 20 years after imatinib: progress and future directions. Nat Rev Drug Discov. 20(7):551-569. https://doi.org/10.1038/s41573-021-00195-4 2.Zhang J, Yang PL, Gray NS (2009). Targeting cancer with small molecule kinase inhibitors. https://doi.org/10.1038/nrc2559 3.Ubersax JA, Ferrell JE, Jr. (2007). Mechanisms of specificity in protein phosphorylation. https://doi.org/10.1038/nrm2203 4.Wallace, DC Mitochondria and Cancer (2012). Nat. Rev. Cancer, 12, 685–698. https://doi.org/10.1038/nrc3365 5.Torres-Quesada O, Strich S, Stefan E (2022). Kinase perturbations redirect mitochondrial function in cancer. BEC 2022.13. https://doi.org/10.26124/bec:2022-0013 6.Torres-Quesada, O, Doerrier, C, Strich, S, Gnaiger, E, Stefan, E (2022). Physiological Cell Culture Media Tune Mitochondrial Bioenergetics and Drug Sensitivity in Cancer Cell Models. Cancers, 14, 3917. https://doi.org/10.3390/cancers14163917 ID: 121
Metabolic stress responses in mitochondrial diseases, ageing and cancer Leukemia cells undergo metabolic remodeling and become vulnerable to mitochondrial translation inhibition University of Miami, United States of America ID: 400
Metabolic stress responses in mitochondrial diseases, ageing and cancer Metabolic reprogramming of bone-marrow mesenchymal stem cells leads to impaired bone formation in m.3243A>G carriers 1Dept. of Endocrinology, Odense University Hospital (OUH), Odense, Denmark; 2The Molecular Endocrinology & Stem Cell Research Unit (KMEB), Molecular Endocrinology, University of Southern (SDU), Denmark; 3Dept. of Molecular Diagnostics, Aalborg University Hospital, Aalborg; 4Department of Biomedicine, Aarhus University, Aarhus, Denmark; 5Khondrion BV, Nijmegen, The Netherlands; 6Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; 7Dept. of Neurology, Rigshospitalet, Copenhagen, Denmark; 8Dept. of Endocrinology, Hospital of Southwest, Esbjerg, Denmark; 9Dept. of Clinical Research, SDU, Denmark; 10Clinical Cell Biology, Dept. of Pathology, OUH, Denmark; 11Dept. of Molecular Medicine, SDU, Denmark; 12Dept. of Forensic Medicine, AU, Denmark; 13Steno Diabetes Centre Odense, OUH, Denmark; 14Dept. of Clinical Genetics, Aalborg University Hospital, Denmark ID: 404
Metabolic stress responses in mitochondrial diseases, ageing and cancer Nucleus Associated Mitochondria (NAM) drive a cholesterol-mediated mechanism of Temozolomide resistance in glioblastoma cells 1Department of Biology, University of Rome Tor Vergata, 00133, Rome, Italy; 2Department of Biophysics, and Centre of Biotechnology, Universida de Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; 3Department of Clinical and Molecular Medicine, University of Rome La Sapienza, 00198 Rome, Italy; 4Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London; 5Department of Biochemistry, Universidade Federal do Rio Grandedo Sul (UFRGS), Porto Alegre, RS, Brazil; 6Department of Neurosurgery, Manchester Academic Health Science Centre, Northern Care Alliance, Salford UK; 7Department of Cellular Pathology, Northern Care Alliance, Salford UK; 8Laboratory of Electron Microscopy, Department of Epidemiology and Preclinical Research National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Rome, Italy; 9Geoffrey Jefferson Brain Research Centre, Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; 10UCL Consortium for Mitochondrial Research, University College London, WC1 6BT, London, UK; 11Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil Bibliography
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Metabolic stress responses in mitochondrial diseases, ageing and cancer Upregulation of COX4-2 via HIF-1α and replicative stress and impaired nuclear DNA damage response in mitochondrial COX4-1 deficiency Hadassah Medical Center and Hebrew University of Jerusalem, Israel Bibliography
Douiev L, Miller C, Keller G, Benyamini H, Abu-Libdeh B, Saada A. Replicative Stress Coincides with Impaired Nuclear DNA Damage Response in COX4-1 Deficiency. Int J Mol Sci. 2022;23(8):4149. Published 2022 Apr 8. doi:10.3390/ijms23084149 Douiev L, Miller C, Ruppo S, Benyamini H, Abu-Libdeh B, Saada A. Upregulation of COX4-2 via HIF-1α in Mitochondrial COX4-1 Deficiency. Cells. 2021;10(2):452. Published 2021 Feb 20. doi:10.3390/cells10020452 Douiev L, Saada A. The pathomechanism of cytochrome c oxidase deficiency includes nuclear DNA damage. Biochim Biophys Acta Bioenerg. 2018;1859(9):893-900. doi:10.1016/j.bbabio.2018.06.004 ID: 221
Metabolic stress responses in mitochondrial diseases, ageing and cancer Analysis of mitochondrial function using novel detection reagents 1DOJINDO LABORATORIES; 2Gunma University ID: 536
Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial dynamics in cancer cells: relationship between the F1Fo-ATPase inhibitor IF1 and the mitochondrial the fusion-fission machinery Department of Biomedical and Neuromotor Sciences, University of Bologna ID: 463
Metabolic stress responses in mitochondrial diseases, ageing and cancer Melatonin overcomes resistance to CDDP treatment associated with the overexpression of the ATP-driven transmembrane efflux pumps 1Institute of Biotechnology; 2Biomedical Research Centre; 3University of Granada, Spain Bibliography
Florido, J., Martínez-Ruíz, L., Rodríguez-Santana, C., López-Rodríguez, A., Hidalgo-Gutiérrez, A., Cottet-Rousselle, C., Lamarche, F., Schlattner, U., Guerra-Librero, A., Aranda-Martínez, P., Acuña-Castroviejo, D., López, L.C., and Escames, G. Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport. Journal of Pineal Research (2022). 73(3). https://doi.org/10.1111/jpi.12824 ID: 250
Metabolic stress responses in mitochondrial diseases, ageing and cancer Therapeutic capacity of exercise and melatonin against inflammation and mitochondrial dysfunction in the iMS-Bmal1-/- model of sarcopenia. 1Departamento de Fisiología, Facultad de Medicina, Centro de Investigación Biomédica (CIBM), Universidad de Granada, Granada, Spain.; 2Instituto de Investigación Biosanitaria de Granada (Ibs.Granada), Granada, Spain.; 3Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid, Spain. Bibliography
Marisol Fernández-Ortiz; Ramy K. A. Sayed; Yolanda Román-Montoya; María Ángeles Rol deLama; José Fernández-Martínez; Yolanda Ramírez-Casas; Javier Florido-Ruiz; Iryna Rusanova;Germaine Escames; Darío Acuña-Castroviejo. Age and Chronodisruption in Mouse Heart: Effectof the NLRP3 Inflammasome and Melatonin Therapy. International Journal of MolecularSciences 2022, 23, 6846. Aranda-Martínez, P.; Fernández-Martínez, J.; Ramírez-Casas, Y.; Guerra-Librero, A.; Rodríguez-Santana, C.; Escames, G.; Acuña-Castroviejo, D. The Zebrafish, an Outstanding Model forBiomedical Research in the Field of Melatonin and Human Diseases. Int. J. Mol. Sci. 2022, 23,7438. https://doi.org/10.3390/ijms23137438 ID: 445
Metabolic stress responses in mitochondrial diseases, ageing and cancer Astrocytic CREB neuroprotection in experimental traumatic brain injury is associated with regulation of energetics and lipid metabolism: role of lactate 1Universitat Autònoma de Barcelona, Institut de Neurociències, Bellaterra, Spain; 2Neurocentre Magendie, Inserm U1215, Bordeaux, France; 3Universitat de Lleida, Institut de Recerca Biomèdica, Lleida, Spain; 4Georgia Institute of Technology, Georgia, United States of America; 5Beatson Institute for Cancer Research, Glasgow, United Kingdom; 6ICREA, Barcelona, Spain Bibliography
Fernández-González, I., & Galea, E. (2022). Astrocyte strategies in the energy-efficient brain. Essays in biochemistry, EBC20220077. Advance online publication. https://doi.org/10.1042/EBC20220077 Navarro-Romero, A., Fernandez-Gonzalez, I., Riera, J., Montpeyo, M., Albert-Bayo, M., Lopez-Royo, T., Castillo-Sanchez, P., Carnicer-Caceres, C., Arranz-Amo, J. A., Castillo-Ribelles, L., Pradas, E., Casas, J., Vila, M., & Martinez-Vicente, M. (2022). Lysosomal lipid alterations caused by glucocerebrosidase deficiency promote lysosomal dysfunction, chaperone-mediated-autophagy deficiency, and alpha-synuclein pathology. NPJ Parkinson's disease, 8(1), 126. https://doi.org/10.1038/s41531-022-00397-6 ID: 164
Metabolic stress responses in mitochondrial diseases, ageing and cancer ROS induced mitochondrial hormesis partially protects from SGAs mitochondrial toxicity and cardiovascular disease. 1Instituto de Investigaciones Biomédicas Alberto Sols, Spain; 2Universidad de Valencia; 3Instituto de Investigación Sanitaria La Princesa; 4CBMSO; 5Universidad Autónoma de Madrid ID: 396
Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial metabolism in breast cancer and cancer-associated adipose tissue 1Institute for Biological Research "Sinisa Stankovic"- National Institute of Republic of Serbia, University of Belgrade, Serbia; 2Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; 3Faculty of Biology, University of Belgrade, Belgrade, Serbia ID: 197
Metabolic stress responses in mitochondrial diseases, ageing and cancer Reorganization of the energy metabolism: from colon polyps to colorectal cancer 1National Institute of Chemical Physics and Biophysics, Estonia; 2North Estonia Medical Centre, Oncology and Haematology Clinic, Tallinn, Estonia Bibliography
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Metabolic stress responses in mitochondrial diseases, ageing and cancer Role of NcoR1 and PGC-1 for mitochondrial dysfunction in skeletal muscle of ovariectomized mice Korea Food Research Institute, Korea, Republic of (South Korea) Bibliography
Mitochondrial dysfunction in skeletal muscle contributes to the development of acute insulin resistance in mice, J Cachexia Sarcopenia Muscle. 2021 Dec;12(6):1925-1939 ID: 431
Metabolic stress responses in mitochondrial diseases, ageing and cancer Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport 1Institute of Biotechnology, Biomedical Research Center, Health Sciences Technology Park, University of Granada, Granada, Spain; 2Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain; 3Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Investigación Biosanitaria (Ibs), Granada, San Cecilio University Hospital, Granada, Spain Bibliography
Martinez-Ruiz, L.; Florido, J.; Rodriguez-Santana, C.; López-Rodríguez, A.; Hidalgo-Gutiérrez, A.; Cottet-Rouselle, C.; Lamarche, F.; Schlattner, U.; Guerra-Librero, A.; Aranda-Martínez, P.; Acuña-Castroviejo, D.; López, LC.; Escames, G.. Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport. Journal of Pineal Research. 28/08/2022. ISSN 1600-079X ID: 537
Metabolic stress responses in mitochondrial diseases, ageing and cancer Differences in life expectancy of rats with inherited high and low exercise capacity correlate with mitochondrial function in skeletal muscle 1University Hospital of Friedrich-Schiller-University Jena, Germany; 2The University of Toledo, Toledo, OH; 3University of Michigan, Ann Arbor, MI ID: 395
Metabolic stress responses in mitochondrial diseases, ageing and cancer Modulation of the activity of human mitochondrial protease complex ClpXP as potential therapeutic strategy for cancer University of Bari "Aldo Moro", Italy Bibliography
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Metabolic stress responses in mitochondrial diseases, ageing and cancer Mitochondrial respiratory function in peripheral blood cells across the human life span 1Lund University, Department of Clinical Sciences Lund, Mitochondrial Medicine, Lund, Sweden; 2Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Otorhinolaryngology, Head and Neck Surgery, Lund, Sweden; 3A&E Department, Kungälv Hospital, Kungälv, Sweden; 4Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark; 5Lund University, Department of Clinical Sciences Lund, Translational Neurology Group and Wallenberg Center for Molecular Medicine, Lund, Sweden; 6Skåne University Hospital, Department of Intensive- and perioperative Care, Malmö, Sweden Bibliography
1. A. Trifunovic et al., Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417-423 (2004). 2. A. Trifunovic et al., Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A 102, 17993-17998 (2005). ID: 607
Clinical 2: natural history, biomarkers and outcome measures Diagnostic value of urine organic acid analysis for primary mitochondrial disorders Research Centre for Medical Genetics, Russian Federation ID: 240
Metabolic stress responses in mitochondrial diseases, ageing and cancer Exercise and melatonin counteract Bmal1 loss-dependent sarcopenia in mouse skeletal muscle by improving mitochondrial ultrastructure and function 1Departamento de Fisiología, Facultad de Medicina, Centro de Investigación Biomédica (CIBM), Universidad de Granada, Granada, Spain.; 2Instituto de Investigación Biosanitaria de Granada (Ibs.Granada), Granada, Spain.; 3Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid, Spain. Bibliography
Fernández-Ortiz, M., Sayed, R. K. A., Román-Montoya, Y., de Lama MÁ, R., Fernández-Martínez, J., Ramírez-Casas, Y., . . . Acuña-Castroviejo, D. (2022). Age and Chronodisruption in Mouse Heart: Effect of the NLRP3 Inflammasome and Melatonin Therapy. Int J Mol Sci, 23(12). doi:10.3390/ijms23126846 Aranda-Martínez, P., Fernández-Martínez, J., Ramírez-Casas, Y., Guerra-Librero, A., Rodríguez-Santana, C., Escames, G., & Acuña-Castroviejo, D. (2022). The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases. Int J Mol Sci, 23(13). doi:10.3390/ijms23137438 Sayed, R. K., Fernández-Ortiz, M., Fernández-Martínez, J., Aranda Martínez, P., Guerra-Librero, A., Rodríguez-Santana, C., . . . Rusanova, I. (2021). The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle. Antioxidants (Basel), 10(4). doi:10.3390/antiox10040524 Sayed, R. K. A., Fernández-Ortiz, M., Rahim, I., Fernández-Martínez, J., Aranda-Martínez, P., Rusanova, I., . . . Acuña-Castroviejo, D. (2021). The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage. Antioxidants (Basel), 10(8). doi:10.3390/antiox10081269 Sayed, R. K. A., Mokhtar, D. M., Fernández-Ortiz, M., Fernández-Martínez, J., Aranda-Martínez, P., Escames, G., & Acuña-Castroviejo, D. (2020). Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging. Aging (Albany NY), 12(13), 12648-12668. doi:10.18632/aging.103654 Fernández-Ortiz, M., Sayed, R. K. A., Fernández-Martínez, J., Cionfrini, A., Aranda-Martínez, P., Escames, G., . . . Acuña-Castroviejo, D. (2020). Melatonin/Nrf2/NLRP3 Connection in Mouse Heart Mitochondria during Aging. Antioxidants (Basel), 9(12). doi:10.3390/antiox9121187 Sayed, R. K. A., Fernández-Ortiz, M., Diaz-Casado, M. E., Aranda-Martínez, P., Fernández-Martínez, J., Guerra-Librero, A., . . . Acuña-Castroviejo, D. (2019). Lack of NLRP3 Inflammasome Activation Reduces Age-Dependent Sarcopenia and Mitochondrial Dysfunction, Favoring the Prophylactic Effect of Melatonin. J Gerontol A Biol Sci Med Sci, 74(11), 1699-1708. doi:10.1093/gerona/glz079 Rusanova, I., Fernández-Martínez, J., Fernández-Ortiz, M., Aranda-Martínez, P., Escames, G., García-García, F. J., . . . Acuña-Castroviejo, D. (2019). Involvement of plasma miRNAs, muscle miRNAs and mitochondrial miRNAs in the pathophysiology of frailty. Exp Gerontol, 124, 110637. doi:10.1016/j.exger.2019.110637 ID: 619
Metabolic stress responses in mitochondrial diseases, ageing and cancer Uncovering the OXPHOS complexes' interdependence mechanism 1Laboratory of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Czech Republic; 2Laboratory of Molecular Therapy of Cancer, Institute of Biotechnology, Czech Academy of Sciences, Vestec, Czech Republic Bibliography
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Clinical 2: natural history, biomarkers and outcome measures Challenging the norm – outcome measure selection for evaluating therapeutic response in patients with Primary Mitochondrial Myopathy after 12 weeks of treatment with REN001, a novel PPARδ agonist. 1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 2National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 4NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 5The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 6Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK ID: 1100
Clinical 2: natural history, biomarkers and outcome measures Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in m.11778G>A MT-ND4 Leber hereditary optic neuropathy patients 1Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 2Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 3IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 4Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 5Sue Anschutz-Rodgers University of Colorado Eye Center, University of Colorado School of Medicine, Aurora, CO, USA; 6Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 7Department of Ophthalmology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan; 8Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 9Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, and Department of Head & Skin, Ghent University, Ghent, Belgium; 10Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; 11Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 12Department of Ophthalmology, Alcala University, Madrid, Spain; 13Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA; 14Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 15GenSight Biologics, Paris, France; 16Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France Bibliography
Newman NJ, Yu-Wai-Man P, Biousse V, Carelli V. Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management. Lancet Neurol. 2022 Sep 22:S1474-4422(22)00174-0. doi: 10.1016/S1474-4422(22)00174-0. Epub ahead of print. PMID: 36155660. Yu-Wai-Man P, Newman NJ, Carelli V, La Morgia C, Biousse V, Bandello FM, Clermont CV, Campillo LC, Leruez S, Moster ML, Cestari DM, Foroozan R, Sadun A, Karanjia R, Jurkute N, Blouin L, Taiel M, Sahel JA; LHON REALITY Study Group. Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study. Eye (Lond). 2022 Apr;36(4):818-826. doi: 10.1038/s41433-021-01535-9. Epub 2021 Apr 28. PMID: 33911213; PMCID: PMC8956580. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. PMID: 34108929; PMCID: PMC8181419. ID: 1451
Clinical 2: natural history, biomarkers and outcome measures The mitochondrial stress, brain imaging, and epigenetics study (MiSBIE) 1Columbia University Irving Medical Center, United States of America; 2Université de Montréal, Canada; 3Université de Bordeaux, France; 4Dartmouth College, Uniter States of America Bibliography
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Inflammation and Immunity as mitochondrial contributor to pathology Free cytosolic-mitochondrial DNA triggers a potent type-I Interferon response in Kearns–Sayre patients counteracted by mofetil mycophenolate 1Unit of Cellular Biology and Diagnosis of Mitochondrial Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; 2Division of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Division of Metabolism, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Research Unit of Muscular and Neurodegenerative Disorders, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy ID: 1409
Inflammation and Immunity as mitochondrial contributor to pathology Fumarate induces mtDNA release via mitochondrial-derived vesicles and drives innate immunity 1Medical Research Council, MBU,University of Cambridge, UK; 2Medical Research Council Cancer Unit,University of Cambridge, UK; 3CECAD Research Centre, University of Cologne, Cologne, Germany Bibliography
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Inflammation and Immunity as mitochondrial contributor to pathology Impaired inflammatory response to lipopolysaccharide in fibroblasts from patients with long-chain fatty acid oxidation disorders 1Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 2Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 3Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark; 4Department of Experimental Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 5Core Facility Metabolomics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands Bibliography
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Metabolic stress responses in mitochondrial diseases, ageing and cancer Functional characterisation of the human mitochondrial disaggregase, CLPB 1Department of Biochemistry and Pharmacology, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville VIC 3010, Australia; 2Murdoch Children’s Research Institute, Royal Children’s Hospital and Department of Paediatrics, The University of Melbourne, Parkville VIC 3052, Australia; 3Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Parkville VIC 3052, Australia ID: 1381
Metabolic stress responses in mitochondrial diseases, ageing and cancer High fat diet ameliorates the mitochondrial cardiomyopathy of CHCHD10 mutant mice Weill Cornell Medicine, United States of America ID: 1448
Metabolic stress responses in mitochondrial diseases, ageing and cancer The mitochondrial inhibitor IF1 has a dual role in cancer 1Department of Biomedical and Neuromotor Sciences, University of Bologna; 2Department of Chemical Science, University of Padova; 3Department of Biology, University of Padova, Padova Bibliography
1. Galber, C; Fabbian, S; Gatto, C; Grandi, M; Carissimi, S; Acosta, MJ; Sgarbi, G; Tiso, N; Argenton, F; Solaini, G; Baracca, A; Bellanda, M; Giorgio,CELL DEATH & DISEASE, 2023, 14, pp. 1 - 19 2. Gatto, C; Grandi, M; Solaini, G; Baracca, A; Giorgio, V, FRONTIERS IN PHYSIOLOGY, 2022, 13, 917203, pp. 1 - 11 3. Galber C; Minervini G; Cannino G; Boldrin F; Petronilli V; Tosatto S; Lippe G; Giorgio V, CELL REPORTS, 2021, 35, 109111, pp. 1 - 14 ID: 657
Clinical 2: natural history, biomarkers and outcome measures Tractography of the anterior optic pathway provides biomarkers of pathological change in Leber’s Hereditary Optic Neuropathy 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy; 2IRCCS Instituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 3Department of Physics and Astronomy, University of Bologna, Italy; 4Department of Life Quality Studies, University of Bologna Bibliography
1 He J, et al. Hum Brain Mapp. 2021 2 Manners DN, et al. Int J Environ Res Public Health. 2022 ID: 661
Metabolic stress responses in mitochondrial diseases, ageing and cancer A novel role of Keap1/PGAM5 complex: ROS sensor for inducing mitophagy 1University of Tartu, Estonia; 2University Paris-Saclay, INSERM UMR-S, France Bibliography
Akbar Zeb, Vinay Choubey, Ruby Gupta, Malle Kuum, Dzhamilja Safiulina, Annika Vaarmann, Nana Gogichaishvili, Mailis Liiv, Ivar Ilves, Kaido Tämm, Vladimir Veksler, Allen Kaasik, A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy, Redox Biology, Volume 48, 2021,102186, ISSN 2213-2317, https://doi.org/10.1016/j.redox.2021.102186. |
| 4:30pm - 6:00pm | Session 3.4: Clinical 2: natural history, biomarkers and outcome measures Location: Bologna Congress Center - Sala Europa Session Chair: Costanza Lamperti Session Chair: Alessandra Maresca |
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Invited
ID: 682 Invited Speakers Optimising interventional trials: how natural history studies and digital technologies can drive innovation 1Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; 2University of Pisa, Italy Invited
ID: 2105 Invited Speakers Identifying circulating biomarkers to monitor mitochondrial disease severity Massachusetts General Hospital, United States of America Oral presentation
ID: 593 Clinical 2: natural history, biomarkers and outcome measures National mitochondrial disease registry in England: linking genetics with routinely collected healthcare data 1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK; 3National Disease Registration Service, NHS Digital, Leeds, UK; 4Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 5NHS Highly Specialised Services for Rare Mitochondrial Disorders – Oxford Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Oral presentation
ID: 157 Clinical 2: natural history, biomarkers and outcome measures Status epilepticus in POLG disease 1Department of Paediatrics and Adolescent Medicine, Haukeland University Hospital, Norway; 2Department of Clinical Medicine (K1), University of Bergen, Norway; 3Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; 4Department of Neuropediatrics, Astrid Lindgren Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden; 5Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 6Department of Paediatric and Adolescent Medicine, University Hospital of North Norway, Tromso, Norway; 7Paediatric Research Group, Department of Clinical Medicine, UiT- The Arctic University of Norway, Tromso, Norway; 8Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway and Unit for Congenital and Hereditary Neuromuscular Disorders, Department of Neurology, Oslo University Hospital, Oslo, Norway; 9Department of Neurology, Oslo University Hospital, Oslo, Norway; 10Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 11Department of Neuroscience and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; 12Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway; 13Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 14Facultiy of Health, Medicine and Life Sciences, Department of Toxicology, , University of Maastricht, Maastricht, The Netherlands; 15Neurometabolic Disorders Unit, Department of Child Neurology/ Department of Genetics and Molecular Medicine, Sant Joan de Déu Children´s Hospital, Barcelona, Spain; 16Department of Pediatric Neurology, Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 17Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; 18Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland; 19Department of Pediatric Neurology, Clinic for Children and Adolescents and Medical Research Center, Oulu University Hospital, Oulu, Finland; 20Research Unit of Clinical Medicine, Neurology, and Medical Research Center Oulu, Oulu University hospital and university of Oulu, Oulu Finland; 21Neurocenter , Oulu University Hospital ,Oulu Finland; 22Movement Disorders Unit, Institut de Recerca Sant Joan de Déu, CIBERER-ISCIII, Barcelona, Spain; 23European Reference Network for Rare Neurological Diseases (ERN-RND), Barcelona, Spain; 24Norwegian national Unit for Newborn Screening, Division of Pediatric and adolescent Medicine, Oslo University Hospital, Oslo, Norway; 25European Reference Network for Hereditary Metabolic Disorder; 26Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway; 27Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 28Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; 29Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK; 30Metabolic Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK; 31Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway Bibliography
Omar Hikmat is a senior consultant in paediatric neurology, working at the Paediatric Neurology section- Paediatric Department, Haukeland University Hospital, Bergen, and researcher at the Mitochondrial Medicine and Neuro-genetic research group, Clinical Institute 1, University of Bergen, Norway. Hikmat has a special interest in paediatric neuro-metabolic, mitochondrial disorders and complex epilepsies. Main research interest is within mitochondrial medicine and particularly the clinical spectrum and natural history of POLG disease. Hikmat is responsible for the National Norwegian POLG registry and the multinational POLG database. Flash Talk
ID: 658 Clinical 2: natural history, biomarkers and outcome measures Challenging the norm – outcome measure selection for evaluating therapeutic response in patients with Primary Mitochondrial Myopathy after 12 weeks of treatment with REN001, a novel PPARδ agonist. 1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 2National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC), Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK; 4NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 5The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 6Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK Flash Talk
ID: 100 Clinical 2: natural history, biomarkers and outcome measures Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in m.11778G>A MT-ND4 Leber hereditary optic neuropathy patients 1Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 2Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 3IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 4Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 5Sue Anschutz-Rodgers University of Colorado Eye Center, University of Colorado School of Medicine, Aurora, CO, USA; 6Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 7Department of Ophthalmology, Taipei Veterans General Hospital, National Yang Ming Chiao Tung University, Taipei, Taiwan; 8Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 9Department of Ophthalmology and Center for Medical Genetics, Ghent University Hospital, and Department of Head & Skin, Ghent University, Ghent, Belgium; 10Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; 11Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 12Department of Ophthalmology, Alcala University, Madrid, Spain; 13Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA; 14Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 15GenSight Biologics, Paris, France; 16Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France Bibliography
Newman NJ, Yu-Wai-Man P, Biousse V, Carelli V. Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management. Lancet Neurol. 2022 Sep 22:S1474-4422(22)00174-0. doi: 10.1016/S1474-4422(22)00174-0. Epub ahead of print. PMID: 36155660. Yu-Wai-Man P, Newman NJ, Carelli V, La Morgia C, Biousse V, Bandello FM, Clermont CV, Campillo LC, Leruez S, Moster ML, Cestari DM, Foroozan R, Sadun A, Karanjia R, Jurkute N, Blouin L, Taiel M, Sahel JA; LHON REALITY Study Group. Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study. Eye (Lond). 2022 Apr;36(4):818-826. doi: 10.1038/s41433-021-01535-9. Epub 2021 Apr 28. PMID: 33911213; PMCID: PMC8956580. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. PMID: 34108929; PMCID: PMC8181419. Flash Talk
ID: 451 Clinical 2: natural history, biomarkers and outcome measures The mitochondrial stress, brain imaging, and epigenetics study (MiSBIE) 1Columbia University Irving Medical Center, United States of America; 2Université de Montréal, Canada; 3Université de Bordeaux, France; 4Dartmouth College, Uniter States of America Bibliography
Picard et al. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress. Proc Natl Acad Sci USA 1;112(48):E6614-23 (2015) https://www.pnas.org/doi/full/10.1073/pnas.1515733112 Karan et al. Leukocyte cytokine responses in adult patients with mitochondrial DNA defects. J Mol Med 100, 963–971 (2022). https://doi.org/10.1007/s00109-022-02206-2 Picard and Shirihai. Mitochondrial signal transduction. Cell Metab 34(11):1620-1653 (2022) https://doi.org/10.1016/j.cmet.2022.10.008 |
| 6:00pm - 7:00pm | Poster session Location: Bologna Congress Center Session topics: - Mitochondrial mechanisms in neurodegeneration and neurodevelopment - The impact of mtDNA variation and environment on rare and common diseases |
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ID: 290
Mitochondrial mechanisms in neurodegeneration and neurodevelopment SARM1 deletion delays cerebellar but not spinal cord degeneration in an enhanced mouse model of SPG7 deficiency 1Institute for Genetics, University of Cologne, Cologne 50931, Germany; 2Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne 50931, Germany; 3Max Planck Institute for Biology of Ageing, Cologne 50931, Germany; 4Center for Molecular Medicine (CMMC), University of Cologne, Cologne 50931, Germany Bibliography
Elsayed LEO, Eltazi IZ, Ahmed AE, Stevanin G. Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview. Frontiers in molecular biosciences. 2021;8:690899. doi:10.3389/fmolb.2021.690899. Figley MD, DiAntonio A. The SARM1 axon degeneration pathway: control of the NAD(+) metabolome regulates axon survival in health and disease. Curr Opin Neurobiol. Aug 2020;63:59-66. doi:10.1016/j.conb.2020.02.012. Figley MD, Gu W, Nanson JD, et al. SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. Neuron. 2021;109(7):1118-1136.e11. doi:10.1016/j.neuron.2021.02.009. König T, Tröder SE, Bakka K, et al. The m-AAA protease associated with neurodegeneration limits MCU activity in mitochondria. Mol Cell. 2016;64(1):148-162. doi:doi: 10.1016/j.molcel.2016.08.020 Koppen M, Metodiev MD, Casari G, Rugarli EI, Langer T. Variable and Tissue-Specific Subunit Composition of Mitochondrial m-AAA Protease Complexes Linked to Hereditary Spastic Paraplegia. Mol Cell Biol. Jan 2007;27(2):758-67. Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. Oct 21 2005;123(2):277-89. ID: 203
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Pathobiology of cerebellar degeneration in the Harlequin mouse, a proteomic and system biology approach 1Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), Madrid, Spain; 2Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Spain.; 3Servicio de Bioquímica Clínica. Hospital Universitario ‘12 de Octubre’. Madrid, Spain; 4Servicio de Genética. Hospital Universitario ‘12 de Octubre’. Madrid, Spain; 5Faculty of Sports Sciences, European University of Madrid, Madrid, Spain; 6Spanish Network for Biomedical Research in Fragility and Healthy Aging (CIBERFES), Madrid, Spain Bibliography
DOI: 10.3390/ijms22126396 DOI: 10.3390/ijms22115598 DOI: 10.3389/fphys.2020.594223 DOI: 10.3389/fneur.2019.00790 DOI: 10.3390/pharmaceutics13020244. DOI: 10.1249/MSS.0000000000001546. ID: 484
Mitochondrial mechanisms in neurodegeneration and neurodevelopment The role of mitochondrial transcriptional processes in the aetiology of Parkinson’s disease 1Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King’s College London, London, United Kingdom; 2Department of Genetics and Genomic Medicine Research & Teaching, UCL GOS Institute of Child Health, London, WC1N 1EH, UK; 3Department of Neurodegenerative Disease, Queen Square Institute of Neurology, UCL, London WC1N 3BG, UK; 4NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, WC1N 1EH, UK; 5Department of Information and Communications Engineering Faculty of Informatics, Espinardo Campus, University of Murcia, Murcia, 30100, Spain ID: 118
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Towards a unitary hypothesis of Alzheimer disease pathogenesis 1Columbia University, USA; 2Centro de Investigaciones Biológicas “Margarita Salas”, Madrid, Spain Bibliography
Area-Gomez E, de Groof AJC, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA (2009). Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am. J. Pathol. 175, 1810-1816. Area-Gomez E, Lara Castillo MdC, Tambini MD, de Groof AJC, Madra M, Ikenouchi J, Umeda M, Bird TD, Sturley SL, Schon EA (2012). Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 31, 4106-4123. Pera M, Larrea D, Guardia-Laguarta C, Montesinos J, Velasco KR, Chan RB, Di Paolo G, Mehler MF, Perumal GS, Macaluso FP, Freyberg ZZ, Acin-Perez R, Enriquez JA, Schon EA, Area-Gomez E (2017). Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease. EMBO J. 36, 3356-3371. ID: 433
Mitochondrial mechanisms in neurodegeneration and neurodevelopment An experimental protocol for in vivo imaging of brain mitochondrial properties with multiphoton microscopy Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal ID: 550
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Exploiting hiPSCs-derived astrocytes from CoPAN patients as cell model to study iron accumulation. 1San Raffaele Scientific Institute; 2Vita-Salute San Raffaele, Italy; 3Fondazione IRCCS Istituto Neurologico Carlo Besta; 4Institute of Neuroscience National Research Council ID: 533
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Secondary mitochondrial impairment in muscle of pediatric patients unrelated to the genes diagnosed by WES: are these mitochondrial diseases? 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 3IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC di Neuropsichiatria dell'Età Pediatrica, Bologna, Italy; 4Child Neuropsychiatry Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 6Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy ID: 377
Mitochondrial mechanisms in neurodegeneration and neurodevelopment In vitro 2D and 3D neuronal model generation of MERRF disease to test therapeutic strategies 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 3Department of Radiological, Oncological and Pathological Sciences, Sapienza, University of Rome, Rome, Italy; 4Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany ID: 186
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Molecular mechanism of human mitochondrial chaperonin and its mutation in neurodegenerative disease Indiana University, United States of America Bibliography
Joseph Wang & Lingling Chen. Structural basis for the structural dynamics of human mitochondrial chaperonin mHsp60. Sci Rep 11, 14809, doi:10.1038/s41598-021-94236-y (2021) Lingling Chen, Aiza Syed and Adhitya Balaji. Hereditary Spastic Paraplegia SPG13 Mutation Increases Structural Stability and ATPase Activity of Human Mitochondrial Chaperonin. Sci Rep 12, 18321, doi:10.1038/s41598-022-21993-9 (2022) ID: 457
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Nucleus-associated mitochondria (NAM) control neuronal Ca2+ signalling and gene expression 1University of Hertfordshire, Department of Clinical, Pharmaceutical and Biological Science, Hatfield, United Kingdom; 2Discovery Research MRL UK, MSD, LBIC, London, United Kingdom; 3William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; 4Proteomics Facility, Centre of Excellence for Mass Spectrometry, King’s College London, London, United Kingdom; 5University of Padua, Department of Biomedical Sciences, Padua, Italy Bibliography
Frison M, Faccenda D, Abeti R, Rigon M, Strobbe D, England-Rendon BS, Cash D, Barnes K, Sadeghian M, Sajic M, Wells LA, Xia D, Giunti P, Smith K, Mortiboys H, Turkheimer FE, Campanella M. The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity. Mol Psychiatry. 2021. 26(7):2721-2739. Singh A*, Faccenda D*, Campanella M. Pharmacological advances in mitochondrial therapy. EBioMedicine. 2021. 65:103244. *Equally contributing authors. Desai R, East DA, Hardy L, Faccenda D, Rigon M, Crosby J, Alvarez MS, Singh A, Mainenti M, Hussey LK, Bentham R, Szabadkai G, Zappulli V, Dhoot GK, Romano LE, Xia D, Coppens I, Hamacher-Brady A, Chapple JP, Abeti R, Fleck RA, Vizcay-Barrena G, Smith K, Campanella M. Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Sci Adv. 2020. 6(51):eabc9955. Strobbe D, Pecorari R, Conte O, Minutolo A, Hendriks CMM, Wiezorek S, Faccenda D, Abeti R, Montesano C, Bolm C, Campanella M. NH-sulfoximine: A novel pharmacological inhibitor of the mitochondrial F1 Fo -ATPase, which suppresses viability of cancerous cells. Br J Pharmacol. 2021. 178(2):298-311. Faccenda D, Gorini G, Jones A, Thornton C, Baracca A, Solaini G, Campanella M. The ATPase Inhibitory Factor 1 (IF1) regulates the expression of the mitochondrial Ca2+ uniporter (MCU) via the AMPK/CREB pathway. Biochim Biophys Acta Mol Cell Res. 2021. 1868(1):118860. Faccenda D, Campanella M. Mitochondria Regulate Inflammatory Paracrine Signalling in Neurodegeneration. J Neuroimmune Pharmacol. 2020. 15(4):565-566. Draper ACE, Wilson Z, Maile C, Faccenda D, Campanella M, Piercy RJ. Species-specific consequences of an E40K missense mutation in superoxide dismutase 1 (SOD1). FASEB J. 2020. 34(1):458-473. ID: 500
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Autophagy controls the pathogenicity of OPA1 mutations in ADOA plus 1Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy; 2Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris, Pisa, Italy Bibliography
1. Carelli, V.; Musumeci, O.; Caporali, L.; Zanna, C.; La Morgia, C.; Del Dotto, V.; Porcelli, A.M.; Rugolo, M.; Valentino, M.L.; Iommarini, L.; et al. Syndromic Parkinsonism and Dementia Associated with OPA 1 Missense Mutations. Ann Neurol. 2015, 78, 21–38, doi:10.1002/ana.24410. 2. Kane, M.S.; Alban, J.; Desquiret-Dumas, V.; Gueguen, N.; Ishak, L.; Ferre, M.; Amati-Bonneau, P.; Procaccio, V.; Bonneau, D.; Lenaers, G.; et al. Autophagy Controls the Pathogenicity of OPA1 Mutations in Dominant Optic Atrophy. J. Cell. Mol. Med. 2017, 21, 2284–2297, doi:10.1111/jcmm.13149. 3. Diot, A.; Agnew, T.; Sanderson, J.; Liao, C.; Carver, J.; Neves, R.P. das; Gupta, R.; Guo, Y.; Waters, C.; Seto, S.; et al. Validating the RedMIT/GFP-LC3 Mouse Model by Studying Mitophagy in Autosomal Dominant Optic Atrophy Due to the OPA1Q285STOP Mutation. Front. Cell Dev. Biol. 2018, 6, 103, doi:10.3389/fcell.2018.00103. ID: 359
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Investigating the function of CHCHD2-CHCHD10 complexes in mitochondria 1Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; 2Department of Neurology, Columbia University Medical Center, New York, NY, USA Bibliography
Nguyen MK*, McAvoy K*, Liao SC, et al. Mouse midbrain dopaminergic neurons survive loss of the PD-associated mitochondrial protein CHCHD2. Hum Mol Genet. 2022;31(9):1500-1518. Sayles NM, Southwell N, McAvoy K, et al. Mutant CHCHD10 causes an extensive metabolic rewiring that precedes OXPHOS dysfunction in a murine model of mitochondrial cardiomyopathy. Cell Rep. 2022;38(10):110475. McAvoy K, Kawamata H. Glial mitochondrial function and dysfunction in health and neurodegeneration. Mol Cell Neurosci. 2019;101:103417. ID: 278
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Sildenafil restores normal MMP in MILS-NPCs with impaired Complex V assembly and activity 1University of Verona, Italy; 2Department of General Pediatrics, Neonatology and Pediatric Cardiology, Duesseldorf University Hospital, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany; 3Charité-Universitätsmedizin Berlin, Department of Neuropediatrics, Berlin, Germany; 4Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico "C.Besta", Milan, Italy; 5Mitochondrial Medicine Laboratory, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy; 6Max Delbrueck Center for Molecular Medicine (MDC), 13125 Berlin, Germany Bibliography
1.Bugiardini E, Bottani E, Marchet S, Poole OV, Beninca C, Horga A, Woodward C, Lam A, Hargreaves I, Chalasani A, Valerio A, Lamantea E, Venner K, Holton JL, Zeviani M, Houlden H, Quinlivan R, Lamperti C, Hanna MG, Pitceathly RDS. Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations. Neurol Genet. 2020 Jan 7;6(1):e381. doi: 10.1212/NXG.0000000000000381. PMID: 32042910; PMCID: PMC6984135. 2.Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Auré K, Leong M, Zabiegalov O, Lyras EM, Pfiffer V, Fauler B, Eichhorst J, Wiesner B, Huebner N, Priller J, Mielke T, Meierhofer D, Izsvák Z, Meier JC, Bouillaud F, Adjaye J, Schuelke M, Wanker EE, Lombès A, Prigione A. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders. Cell Stem Cell. 2017 May 4;20(5):659-674.e9. doi: 10.1016/j.stem.2016.12.013. Epub 2017 Jan 26. PMID: 28132834. 3.Lorenz C, Zink A, Henke MT, Staege S, Mlody B, Bünning M, Wanker E, Diecke S, Schuelke M, Prigione A. Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6. Stem Cell Res. 2022 May; 61:102742. doi: 10.1016/j.scr.2022.102742. Epub 2022 Mar 8. PMID: 35279592. 4.Wang X, Fisher PW, Xi L, Kukreja RC. Essential role of mitochondrial Ca2+-activated and ATP-sensitive K+ channels in sildenafil-induced late cardioprotection. J Mol Cell Cardiol. 2008 Jan;44(1):105-13. doi: 10.1016/j.yjmcc.2007.10.006. Epub 2007 Oct 16. PMID: 18021798. ID: 202
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial dysfunction due to mRNA transport defects as a mechanism of neurodegeneration? Unraveling the role of TBCK in a human neuronal model 1Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia; 2Division of Neurology, The Children's Hospital of Philadelphia ID: 231
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Modelling COASY protein-associated neurodegeneration (CoPAN) in mice IRCCS Istituto Neurologico C. Besta, Italy Bibliography
- Di Meo I, Cavestro C, Pedretti S, et al. Neuronal Ablation of CoA Synthase Causes Motor Deficits, Iron Dyshomeostasis, and Mitochondrial Dysfunctions in a CoPAN Mouse Model. Int J Mol Sci. 2020;21(24):9707. Published 2020 Dec 19. - Cavestro C, Panteghini C, Reale C, et al. Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson's disease with brain iron accumulation through pseudo-exon activation. Neurogenetics. 2021;22(4):347-351 - Santambrogio P, Ripamonti M, Cozzi A, et al. Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype. Cell Death Dis. 2022;13(2):185. Published 2022 Feb 25 - Zanuttigh E, Derderian K, Güra MA, et al. Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro. Pharmaceutics. 2023;15(1):267. Published 2023 Jan 12 - Santambrogio P, Cozzi A, Di Meo I, et al. PPAR Gamma Agonist Leriglitazone Recovers Alterations Due to Pank2-Deficiency in hiPS-Derived Astrocytes. Pharmaceutics. 2023;15(1):202. Published 2023 Jan 6. doi:10.3390/pharmaceutics15010202 ID: 644
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Neural stem cell niche-interactions in mitochondrial disease University of Cambridge, United Kingdom ID: 398
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q 1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy, 40138; 2U.O. Genetica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, 40138; 3Center for Applied Biomedical Research (CRBA), University of Bologna, Bologna, Italy, 40138; 4Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy, 40126; 5Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany, 45122; 6Department of Veterinary Sciences, University of Bologna, Bologna, Italy, 40064; 7Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany, 72076; 8Center for Rare Diseases, University of Tübingen, Tübingen, Germany, 72076; 9Department of Pediatric Neurology, Centre for Neuromuscular Disorders, Centre for Translational Neuro- and Behavioral Sciences, University Duisburg-Essen, Essen, Germany, 45122 ID: 576
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Characterization of a novel brain-specific mouse model of Leigh Syndrome Neuroscience Institute-Autonomous University of Barcelona, Spain Bibliography
(1) N. J. Lake et al., Ann. Neurol. 79:190-203 (2016). (2) C. Garone, C. Viscomi, Biochem. Soc. Trans. 46, 1247–1261 (2018). (3) A. Quintana et al., Proc. Natl. Acad. Sci. U. S. A. 107, 10996–11001 (2010). (4) C. Viscomi et al., Cell Metab, 14, 80–90. (2011). ID: 630
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Investigating FA physiopathology in human iPSC-derived DRG organoïds 1Institut NeuroMyoGene, PGNM UMR5261, INSERM U1315, Université Claude Bernard Lyon I Faculté de médecine Rockefeller, Lyon 08 France; 2UT Southwestern Medical Center, 5323 Harry Hines Blvd. Suite NL.9.108 TX75390-8813 Dallas USA ID: 214
Mitochondrial mechanisms in neurodegeneration and neurodevelopment A novel TUBB2A variant associated with pediatric neurodegeneration links microtubule stability to mitochondrial function 1Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia; 2Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia; 3Department of Radiology, The Children’s Hospital of Philadelphia; 4Department of Pathology and Cell Biology, Columbia University ID: 487
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Characterization and functional analysis of a zebrafish knockdown of the mitochondrial DNA replication gene ssbp1 1Institute for Neurosciences of Montpellier (INM) U1298, France; 2Molecular Mechanisms in Neurodegenerative Dementia (MMDN) U1198, France Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Deep mitochondrial genotyping reveals altered mitochondrial quality control mechanisms in advanced cellular models of Parkinson’s disease Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Defining the nuclear genetic architecture of a maternally-inherited mitochondrial disorder 1Wellcome Centre for Mitochondrial Research and Institute for Translational and Clinical Research, ewcastle University, United Kingdom; 2NHS Highly Specialised Mitochondrial Diagnostic Laboratory, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU Klinikum), Munich, Germany; 4Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; 5Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; 6Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; 7Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 8German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 9Department of Neurology, University Hospital Bonn, Bonn, Germany; 10Neurological Institute of Pisa, Italy; 11Institute of Human Genetics, School of Medicine, Technische Universität München, München, Germany; 12Institute of Neurogenomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany; 13Department of Neurology, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 14Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany; 15Neurogenetics Unit, The National Hospital for Neurology and Neurosurgery, London, UK; 16Population Health Sciences Institute, Newcastle University, UK Bibliography
Boggan, R. M., Ng, Y. S., Franklin, I. G., Alston, C. L., Blakely, E. L., Büchner, B., Bugiardini, E., Colclough, K., Feeney, C., Hanna, M. G., Hattersley, A. T., Klopstock, T., Kornblum, C., Mancuso, M., Patel, K. A., Pitceathly, R. D. S., Pizzamiglio, C., Prokisch, H., Schäfer, J., … Pickett, S. J. (2022). Defining the nuclear genetic architecture of a common maternally inherited mitochondrial disorder. In medRxiv (p. 2022.11.18.22282450). https://doi.org/10.1101/2022.11.18.22282450 Boggan, R. M., Lim, A., Taylor, R. W., McFarland, R., & Pickett, S. J. (2019). Resolving complexity in mitochondrial disease: Towards precision medicine. Molecular Genetics and Metabolism, 128(1-2), 19–29. ID: 375
Mitochondrial mechanisms in neurodegeneration and neurodevelopment OPA3 loss causes alterations in mitocondrial dynamics and autophagy processes 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, via Altura 3, 40139, Bologna, Italy; 2Department of Biomedical and NeuroMotor Sciences, University of Bologna, via Altura 3, 40139, Bologna, Italy ID: 481
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial fusion- and transport-specific roles in neuronal dysfunction 1Institute for Biochemistry, University of Cologne, Cologne, Germany; 2Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany ID: 468
Mitochondrial mechanisms in neurodegeneration and neurodevelopment ER-Mitochondria are affected during ageing in enteric neurons Inserm U1235, France Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Identification of dysregulated molecular pathways in Frataxin deficient Proprioceptive Neurons INMG-PGNM, France ID: 387
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial dysfunction in dorsal root ganglia in Friedreich ataxia mouse and cell models: role of SirT3 Dept. Ciències Mèdiques Bàsiques, Fac. Medicina, Universitat de Lleida. IRBLleida. Lleida (Spain). ID: 239
Mitochondrial mechanisms in neurodegeneration and neurodevelopment MPTP-induced parkinsonism in zebrafish provokes chronodisruption-related loss of daily melatonin and locomotor activity rhythms and mitochondrial dynamics shift, which are restored by melatonin treatment 1Departamento de Fisiología, Facultad de Medicina, Centro de Investigación Biomédica (CIBM), Universidad de Granada, Granada, Spain.; 2Instituto de Investigación Biosanitaria de Granada (Ibs.Granada), Granada, Spain.; 3Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid, Spain. Bibliography
Javier Florido Ruiz; Laura Martínez Ruiz; César Rodríguez Santana; Alba López Rodríguez; Agustín Hidalgo Gutiérrez; Cécile Cottet Rousselle; Frédéric Lamarche; Uwe Schlattner; Ana Guerra-Librero Rite; Paula Aranda Martínez; Darío Acuña Castroviejo; Luis Carlos López García; Germaine Escames. Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport.Journal of Pineal Research. 73 - 3, pp. e12824. 03/10/2022. Paula Aranda Martínez; Jose Fernández Martínez; Yolanda Ramírez Casas; Ana Guerra-Librero Rite; César Rodríguez Santana; Germaine Escames; Darío Acuña Castroviejo. The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases.International Journal of Molecular Sciences. 23 - 13, pp. 7438. MPDI, 04/07/2022. Rammy Sayed; Marisol Fernández Ortiz; Ibtissem Rahim; Jose Fernández Martínez; Paula Aranda Martínez; Iryna Rusanova; Laura Martínez Ruiz; Reem M Alsaadawy; Germaine Escames; Darío Acuña Castroviejo. The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage. Antioxidants. 10 - 8, pp. 1269. 10/08/2021. Rammy Sayed; Marisol Fernández Ortiz; Jose Fernández Martínez; Paula Aranda Martínez; Ana Guerra-Librero Rite; César Rodríguez Santana; Tomás de Haro; Germaine Escames; Darío Acuña Castroviejo; Iryna Rusanova. The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle. Antioxidants. 10 - 4, pp. 524. 27/03/2021 ID: 360
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Activation of integrated mitochondrial stress response in PRKN Parkinson Disease 1Inherited metabolic diseases and muscular disorders Lab, Cellex - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science - University of Barcelona (UB), Department of Internal Medicine - Hospital Clínic of Barcelona (HCB), 08036 Barcelona, Spain, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, U722), 28029 Madrid, Spain.; 2Research Program of Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland; HUSlab, Helsinki University Hospital, Helsinki 00290, Finland;; 3Laboratory of Parkinson Disease and Other Neurodegenerative Movement Disorders, IDIBAPS-Hospital Clínic de Barcelona, Institut de Neurociències, UB, 08036 Barcelona, Spain and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED CB06/05/0018), 28029 Madrid, Spain.; 4Department of Clinical Biochemistry, Institut de Recerca de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain, and CIBERER, 28029 Madrid, Spain.; 5Department of Statistics, Biology Faculty, UB, Barcelona, Spain; 6Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain; Department of Biochemistry and Molecular Biomedicine, UB, E-08028 Barcelona, Spain; U731, CIBERER, 08028 Barcelona, Spain; ID: 159
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Delineating the neurodegenerative mechanisms underpinning epilepsy in Alpers’ syndrome 1Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; 2Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; 3NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK Bibliography
Smith LA, Erskine D, Blain A, Taylor RW, McFarland R, Lax NZ. Delineating selective vulnerability of inhibitory interneurons in Alpers' syndrome. Neuropathol Appl Neurobiol. 2022:e12833. ID: 148
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Understanding the effects of hyperbaric oxygen therapy on Alzheimer’s disease mouse model Tel-Aviv University, Israel Bibliography
Schottlender, N., Gottfried, I., Ashery, U. Hyperbaric oxygen therapy: effects on mitochondrial function and oxidative stress (2022). Biomolecules. 11. 1827. doi: 10.3390/biom11121827 Gottfried, I., Schottlender, N., Ashery, U. Hyperbaric oxygen therapy – from Mechanism to Cognitive Improvement. (2021). Biomolecules. 11(10). 1520. doi: 10.3390/biom11101520 Rimmerman, N., Verdiger, H. Ryan, K. M., Goldenberg, H., Naggan, L., Robinson, E., Reshef, R., Ayoun, L., Refaeli, R., Ashkenazi, E., Schottlender, N., Ben Hemo-Cohen, L., Pienica, C., Abargyl, M., Lazar, K., McLoughlin, D. M., Yirmiya, R (2021). Microglia and their LAG-3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive therapy (ECT). Molecular Psychiatry. doi: 10.1038/s41380-021-01338-0 Shvarts-Serebro, I., Sheinin, A., Gotfried, I., Schottlender, N., Adler, L., Ashery, U., Barak, B. (2021). miR-128 as a Regulator of Synaptic Properties in 5xFAD Mice Hippocampal Neurons. Journal of Molecular Neuroscience. 71 (12): 2593-2607. doi: 10.1007/s12031-021-01862-2 Radomir, L., Kramer, M. P., Perpinial, M., Schottlender, N., Rabani, S., David, K., Weiner, A., Lewinsky, H., Becker Hermann, S., Aharoni, R., Milo, R., Claduai, M. and Shachar, I. (2021). The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nature communications. 12. 1893. doi: 10.1038/s41467-021-22230-z Aharoni, R., Eilam, R. Schottlender, N., Radomir, L., Leistner Segal, S., Feferman, T., Hirsch, D., Sela, M. and Arnon, R. (2020). Glatiramer acetate increases T- and B -regulatory cells and decreases granulocyte-macrophage colony-stimulating factor (GM-CSF) in an animal model of multiple sclerosis. Journal of Neuroimmonology. 345. doi: 10.1016/j.jneuroim.2020.577281. Sever, L., Radomir, L., Strim, K., Wiener A., Schottlender, N., Lewinsky, H., Barak, A., Friedlander, G., Ben-Dor, S., Shay, T., Becker Hermann, S. and Shachar, I. (2019). SLAMF9 regulates pDCs homeostasis and function in health and disease. PNAS. doi: 10.1073/pnas.1900079116. Aharoni, R., Schottlender, N., Bar Lev, D. D., Tsoory, M., Sela, M., and Arnon, R. (2019). The effect of Glatiramer Acetate (GA) on cognitive function in an animal model of multiple sclerosis. Scientific Reports. 9:4140. doi: 10.1038/s41598-019-40713-4. Rimmerman, N., Schottlender, N. Reshef, R., Dan-Goor, N., and Yirmiya, R. (2017). The hippocampal transcriptome signature of stress resilience in mice with microglial fractalkine receptor (CX3CR1) deficiency. Brain, Behavior and Immunity. 61: 184-196. doi: 10.1016/j.bbi.2016.11.023. ID: 252
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Analyzing the mitochondrial HPDL protein in fish and human models IRCCS Fondazione Stella Maris, Italy ID: 187
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Modulation of mitophagy, mitochondrial and autophagy phenotypes in LRRK2 Parkinson’s patient fibroblast-derived dopaminergic neurons by small molecules 1Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, Sheffield, UK.; 2Verge Genomics, South San Francisco, CA, USA. ID: 384
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Proinflammatory cytokines induce alterations of mitochondrial functions and dynamics in neurons Institute of Neuroscience, National Chengchi University, Taiwan ID: 106
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial dysfunction is involved in progranulin-related frontotemporal dementia 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2Neurogenetics Unit, Rare and Inherited Disease Genomic Laboratory, North Thames Genomic Laboratory Hub, London, UK; 3Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; 4Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; 5Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Royal Free Campus, London, UK; 6NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Morphological characterization of the progression of mitochondrial encephalopathy associated with CoQ10 deficiency 1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Biofisika Institute (CSIC, UPV-EHU) and Department of Biochemistry and Molecular Biology, University of Basque Country, Leioa, Spain; 3Ibs.Granada, Granada, Spain Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment The vanishing dopamine in Parkinson’s disease IST Austria, Austria Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Effect of UPO04 depending on GAA triplet hyperexpansion in Friedreich’s ataxia disease. Universidad Pablo de Olavide, Spain Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment New cell model for studying mitochondrial dysfunction in Fragile X-associated tremor/ataxia syndrome Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland ID: 191
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Development of an in vitro platform for preclinical investigations on EPM1 1University of Eastern Finland, Finland; 2Kuopio University Hospital, Finalnd ID: 579
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Metabolic rewiring in iPSCs-derived neuron progenitor cells of patients with mutations of mitochondrial SLC25A12/AGC1 carrier 1Department of Biosciences Biotechnologies and Environment, University of Bari, Italy; 2Department of Pharmacy and BioTechnology, University of Bologna, Italy; 3Institute of Human Genetics, University Hospital, Leipzig, Germany; 4Hematology and Cell Therapy Unit, IRCCS-Istituto Tumori "Giovanni Paolo II, Bari, Italy; 5Children's Hospital of Philadelphia Research Institute, Philadelphia, USA; 6University Children's Hospital, Heinrich-Heine-University, Düsseldorf, Germany Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial function at the neuromuscular junction in motor neuron disease 1Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom; 2Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK; 3The Francis Crick Institute, London, UK. ID: 228
Mitochondrial mechanisms in neurodegeneration and neurodevelopment A novel WDR45 variant in an encephalopathy mimicking Leigh syndrome with complex I deficiency 1Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.; 2Department of Health Sciences,University of Milan, Milan, Italy; 3Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy ID: 142
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Characterisation of mitochondrial dysfunction in Huntington’s disease patient-derived fibroblasts 1University of Sheffield, Sheffield Institute for Translational Neuroscience, United Kingdom; 2Nanna Therapeutics, Cambridge, UK ID: 543
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Loss of mitochondrial chaperone Trap1 in mice causes changes in synaptic mitochondria function Centre of New Technologies, University of Warsaw, Poland ID: 435
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Unveiling the metabolic signature of synaptic mitochondria Instituto de Medicina Molecular João Lobo Antunes, Portugal Bibliography
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Mitochondrial mechanisms in neurodegeneration and neurodevelopment Aberration of mitochondrial ultrastructure in the skeletal muscle in patients with Parkinson’s disease 1Neurocenter, Oulu University Hospital, Oulu, Finland; 2Research Unit of Clinical Medicine, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu Finland; 3Electron microscopy, Biocenter Oulu, University of Oulu, Oulu, Finland; 4Pathology, Turku University Hospital and University of Turku, Turku, Finland; 5Pathology, Oulu University Hospital, Oulu, Finland; 6Division of Orthopaedic and Trauma Surgery, Department of Surgery, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland Bibliography
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The impact of mtDNA variation and environment on rare and common diseases New insights into the pathogenicity of the MT-ATP6: m.9176T>C mutation by a patient cohort and transmitochondrial cybrids combined approach 1Mitochondrial Diseases Laboratory, Research Institute, Universitary Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain.; 2Department of Pediatric Neurology, Hospital General Universitario de Toledo, Toledo, Spain.; 3Biochemistry Department, Biomedical Research Institute 'Alberto Sols', CSIC, Faculty of Medicine, Autonomous University of Madrid, and Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain.; 4iPS Cells Translational Research Group, Research Institute, Universitary Hospital 12 de Octubre (Imas12), 28041 Madrid, Spain.; 5Centre for Biomedical Network Research on Rare Diseases (CIBERER), Spain. Bibliography
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The impact of mtDNA variation and environment on rare and common diseases Determining the contribution of mitochondrial alterations to lung cancer in vivo Karolinska Institute, Sweden Bibliography
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The impact of mtDNA variation and environment on rare and common diseases Gamma Peptide Nucleic Acids as a Mechanism for Targeting the Mitochondrial Genome 1Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; 2Department of Medicine, Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; 3Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA; 4Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts, USA Bibliography
Farmerie L, Rustandi RR, Loughney JW, Dawod M. Recent advances in isoelectric focusing of proteins and peptides. J Chromatogr A. 2021 Aug 16;1651:462274. doi: 10.1016/j.chroma.2021.462274. Epub 2021 May 24. PMID: 34090060. ID: 604
The impact of mtDNA variation and environment on rare and common diseases Physiological variability in mitochondrial rRNA may predispose to metabolic syndrome 1Laboratory of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 2Laboratory of Genetics of Model Diseases, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 3Laboratory of Translational Metabolism, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic ID: 590
The impact of mtDNA variation and environment on rare and common diseases The European landscape of mitogenomes from LHON patients carrying the m.14484T>C/MT-ND6 pathogenic variant 1University of Bologna, Italy; 2University of Pavia, Pavia, Italy; 3Laboratory of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, Rome, Italy; 4IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; 5University of Tuebingen, Tuebingen, Germany; 6Université LUNAM, Angers, France; 7Universidad de Zaragoza, Zaragoza, Spain; 8National Neurological Institute 'C. Besta', Milano, Italy; 9Ludwig-Maximilians-Universität München, Munich, Germany; 10UCLA, Los Angeles, California, USA; 11University of Siena, Siena, Italy; 12University of Newcastle, Newcastle upon Tyne, UK; 13University of Cambridge, Cambridge, UK; 14Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK; 15Erasmus Medical Centre, Rotterdam, The Netherlands; 16PhD, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna ID: 458
The impact of mtDNA variation and environment on rare and common diseases Mitochondrial DNA contribution to Parkinsonism: from mtDNA maintenance defects to primary mtDNA pathogenic variants 1IRCCS Istituto delle Scienze Neurologiche, Italy; 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy ID: 460
The impact of mtDNA variation and environment on rare and common diseases Combined fiber atrophy and impaired muscle regeneration capacity driven by mitochondrial DNA alterations underlie the development of sarcopenia 1Department of Medical Laboratory Sciences, Masinde Muliro University of Science and Technology - Kakamega, Kenya; 2Institute of Vegetative Physiology, University of Cologne - Cologne, Germany; 3Max Planck Institute for Heart and Lung Research - Bad Nauheim, Germany; 4Institute for Cardiovascular Physiology, University Medical Center - Göttingen, Germany; 5Institute of Physiology I, Medical Faculty, University of Bonn - Bonn, Germany; 6Center for Molecular Medicine Cologne - Cologne, Germany; 7Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) - Cologne, Germany; 8University of Angers, UMR 6015 CNRS / 1083 INSERM, Mitovasc - Angers, France ID: 291
The impact of mtDNA variation and environment on rare and common diseases Examining the link between diet and metabolic risk score in individuals with bipolar disorder University of Toronto, Canada Bibliography
Kuang H, Duong A, Jeong H, Zachos K, Andreazza AC. Lactate in bipolar disorder: a systematic review and meta-analysis. Psychiatry Clin Neurosci. 2018. ID: 254
The impact of mtDNA variation and environment on rare and common diseases Mitochondrial morphology and function in mitochondrial disease 1Newcastle University, United Kingdom; 2Welcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; 3NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne, United Kingdom Bibliography
The AIMM Trial Group (2022). “Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded placebo-controlled, adaptive design trial of the efficacy of Acipimox in adult patients with mitochondrial myopathy.” Trials. 23(1). Mito, T., Vincent, A.E., Faitg, J., Taylor, R.W., Khan, N., McWilliam, T.G., Suomalainen, A. “Mosaic dysfunction of mitophagy in mitochondrial disease”. Cell Metabolism.34: 1-12. Faitg, J., Lacefield, C., Davey, T., White, K., Laws, R., Kosmidis, S., Reeve, A.K., Kandel, E.R., Vincent, A.E.*, Picard, M*. (2021) “3D Neuronal Mitochondrial Morphology in Axons Dendrites and Somata of the Ageing mouse Hippocampus”. Cell Reports. 36:109509. Faitg, J., Davey, T., Turnbull, D.M., White, K., Vincent, A.E. (2020) “Mitochondrial morphology and function: Two for the price of one”. Journal of Microscopy. 278(2):89-106. ID: 620
The impact of mtDNA variation and environment on rare and common diseases MtDNA sequence and copy number analysis of buffy coat DNA of primary open-angle glaucoma patients 1University Eye Clinic Maastricht, Maastricht University Medical Center+, Maastricht, The Netherlands; 2Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands; 3School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; 4Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands; 5Department of Dermatology, GROW-school for oncology and reproduction, Maastricht University Medical Center, Maastricht, The Netherlands ID: 592
The impact of mtDNA variation and environment on rare and common diseases MELAS syndrome pathophysiology in cellular models of the disease Universidad Pablo de Olavide, Spain ID: 349
The impact of mtDNA variation and environment on rare and common diseases Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease 1Otorhinolaryngology, Head and Neck Surgery, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Sweden; 2Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, USA; 3Logopedics, Phoniatrics and Audiology, Department of Clinical Sciences Lund, Lund University, Sweden; 4Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, USA; 5Division of Biostatistics, Department of Pediatrics, Children's Hospital of Philadelphia, USA; 6Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University, Sweden ID: 612
The impact of mtDNA variation and environment on rare and common diseases What can we learn from detrimental mitogenome mutations in cattle? 1University of Zagreb - Faculty of Agriculture, 10000 Zagreb, Croatia; 2University of Ljubljana - Veterinary Faculty, 1000 Ljubljana, Slovenia; 3University of Ljubljana - Biotechnical Faculty, 1000 Ljubljana, Slovenia; 4Croatian Veterinary Institute, 10000 Zagreb, Croatia; 5Agricultural Institute of Slovenia, 1000 Ljubljana, Slovenia ID: 312
The impact of mtDNA variation and environment on rare and common diseases Mitochondrial DNA copy number measurements reveal systemic evidence for mitochondrial dysfunction in age-related macular degeneration 1Medical University of Innsbruck, Austria; 2University of Regensburg, Germany ID: 114
The impact of mtDNA variation and environment on rare and common diseases Multiple mitochondrial DNA deletions in patients with myopathy 1Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; 2Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA ID: 363
The impact of mtDNA variation and environment on rare and common diseases Utilizing donor mitochondrial haplogroup as a potential screening tool for the risk of primary graft dysfunction 1University of Toronto, Canada; 2University Health Network, Toronto Bibliography
Abdelnour-Berchtold, E., Ali, A., Baciu, C., Beroncal, E. L., Wang, A., Hough, O., Kawashima, M., Chen, M., Zhang, Y., Liu, M., Waddell, T., Andreazza, A. C., Keshavjee, S., & Cypel, M. (2022). Evaluation of 10°C as the optimal storage temperature for aspiration-injured donor lungs in a large animal transplant model. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 41(12), 1679–1688. https://doi.org/10.1016/j.healun.2022.08.025 Ali, A., Nykanen, A. I., Beroncal, E., Brambate, E., Mariscal, A., Michaelsen, V., Wang, A., Kawashima, M., Ribeiro, R. V. P., Zhang, Y., Fan, E., Brochard, L., Yeung, J., Waddell, T., Liu, M., Andreazza, A. C., Keshavjee, S., & Cypel, M. (2022). Successful 3-day lung preservation using a cyclic normothermic ex vivo lung perfusion strategy. EBioMedicine, 83, 104210. https://doi.org/10.1016/j.ebiom.2022.104210 Ali, A., Wang, A., Ribeiro, R. V. P., Beroncal, E. L., Baciu, C., Galasso, M., Gomes, B., Mariscal, A., Hough, O., Brambate, E., Abdelnour-Berchtold, E., Michaelsen, V., Zhang, Y., Gazzalle, A., Fan, E., Brochard, L., Yeung, J., Waddell, T., Liu, M., Andreazza, A. C., … Cypel, M. (2021). Static lung storage at 10°C maintains mitochondrial health and preserves donor organ function. Science translational medicine, 13(611), eabf7601. https://doi.org/10.1126/scitranslmed.abf7601 ID: 313
The impact of mtDNA variation and environment on rare and common diseases A rare variant m.4135T>C in the MT-ND1 gene leads to LHON and altered OXPHOS supercomplexes 1Department of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic; 2Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; 3Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic. ID: 283
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitophagy is stalled in cultured fibroblasts harbouring Parkin mutations 1Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK.; 2Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USA.; 3Signalling Programme. The Babraham Institute, Cambridge, UK. ID: 662
The impact of mtDNA variation and environment on rare and common diseases Impact of mitochondrial DNA modifications in shaping personalized ETC complex activities 1University of Oslo, Norway; 2Oslo University Hospital ID: 477
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Elucidating the role of ATF3 in the neuropathology of a mouse model of Leigh Syndrome 1Institut de Neurociències, Universitat Autònoma de Barcelona. Bellaterra (Barcelona) 08193. Spain; 2Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona. Bellaterra (Barcelona) 08193. Spain ID: 541
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Deciphering the contribution of the Parvalbumin-expressing neurons in the motor, cognitive and social alterations in a mouse model of Leigh Syndrome 1Autonomous University of Barcelona, Bellaterra, Spain; 2Scripps Research, La Jolla, CA, USA Bibliography
Cutando L, Puighermanal E, Castell L, Tarot P, Belle M, Bertaso F, Arango-Lievano M, Ango F, Rubinstein M, Quintana A, Chédotal A, Mameli M, Valjent E. Cerebellar dopamine D2 receptors regulate social behaviors. Nat Neurosci. 2022 Jul;25(7):900-911. doi: 10.1038/s41593-022-01092-8. Epub 2022 Jun 16. PMID: 35710984. Cutando L, Puighermanal E, Castell L, Tarot P, Bertaso F, Bonnavion P, de Kerchove d'Exaerde A, Isingrini E, Galante M, Dallerac G, Pascoli V, Lüscher C, Giros B, Valjent E. Regulation of GluA1 phosphorylation by d-amphetamine and methylphenidate in the cerebellum. Addict Biol. 2021 Jul;26(4):e12995. doi: 10.1111/adb.12995. Epub 2020 Dec 26. PMID: 33368923. Martínez-Torres S*, Cutando L*, Pastor A, Kato A, Sakimura K, de la Torre R, Valjent E, Maldonado R, Kano M, Ozaita A. Monoacylglycerol lipase blockade impairs fine motor coordination and triggers cerebellar neuroinflammation through cyclooxygenase-2. Brain Behav Immun. 2019 Oct;81:399-409. doi: 10.1016/j.bbi.2019.06.036. Epub 2019 Jun 25. PMID: 31251974. * First co-authors. Cutando L, Busquets-Garcia A, Puighermanal E, Gomis-González M, Delgado-García JM, Gruart A, Maldonado R, Ozaita A. Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure. J Clin Invest. 2013 Jul;123(7):2816-31. doi: 10.1172/JCI67569. Epub 2013 Jun 24. PMID: 23934130; PMCID: PMC3696568. ID: 267
Mitochondrial mechanisms in neurodegeneration and neurodevelopment CHCHD10 and SLP2 control the stability of the PHB complex : a key factor for motor neuron viability 1Université Côte d’Azur, Inserm U1081, CNRS UMR7284, IRCAN, CHU de Nice, Nice (France); 2Mitochondrial Biology Group, Institut Pasteur, CNRS UMR 3691, Paris (France); 3Université Côte d’Azur, Centre Commun de Microscopie Appliquée, Nice (France); 4Mécanismes Centraux et Périphériques de la Neurodégénérescence, Inserm U1118, UMR S1118, CRBS, Université de Strasbourg, Strasbourg (France) Bibliography
- Genin EC*, Bannwarth S*, Ropert B, Lespinasse F, Mauri-Crouzet A, Augé G, Fragaki K, Cochaud C, Donnarumma E, Lacas-Gervais S, Wai T, Paquis-Flucklinger V. CHCHD10 and SLP2 control the stability of the PHB complex : a key role factor for motor neuron viavility. Brain 2022 Oct 21 ;145(10) :3415-3430. doi : 10.1093/brain/awac197 - Genin EC*, Madji Hounoum B*, Bannwarth S, Fragaki K, Lacas-Gervais S, Mauri-Crouzet A, Lespinasse F, Neveu J, Ropert B, Augé G, Cochaud C, Lefebvre-Omar C, Bigou S, Chiot A, Mochel F, Boillée S, Lobsiger CL, Bohl D, Ricci J-E, Paquis-Flucklinger V. Mitochondrial defect in muscle precedes neuromuscular junction degeneration and motor neuron death in CHCHD10S59L/+ mouse. Acta Neuropathologica, 2019 Jul;138(1) :123-145. doi: 10.1007/s00401-019-01988-z ID: 280
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial dysfunction in peripheral blood mononuclear cells in different stages of Huntington´s disease 1Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; 2Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; 3Department of Medical Biochemistry, University of Oslo and Oslo University Hospital, Oslo, Norway. Bibliography
Bibliography of Vanisova ( Rodinova) Marie: Vanisova M, Stufkova H, Kohoutova M, Rakosnikova T, Krizova J, Klempir J, Rysankova I, Roth J, Zeman J, Hansikova H. Mitochondrial organization and structure are compromised in fibroblasts from patients with Huntington's disease. Ultrastruct Pathol. 2022 Aug 10:1-14. doi: 10.1080/01913123.2022.2100951. Rodinova M, Krizova J, Stufkova H, Bohuslavova B, Askeland G, Dosoudilova Z, Juhas S, Juhasova J, Ellederova Z, Zeman J, Eide L, Motlik J, Hansikova H. Skeletal muscle in an early manifest transgenic minipig model of Huntington's disease revealed deterioration of mitochondrial bioenergetics and ultrastructure impairment.Dis Model Mech. 2019 Jul 5. pii: dmm.038737. doi: 10.1242/dmm.038737. Skalnikova HK, Bohuslavova B, Turnovcova K, Juhasova J, Juhas S, Rodinova M, Vodicka P. Isolation and Characterization of Small Extracellular Vesicles from Porcine Blood Plasma, Cerebrospinal Fluid, and Seminal Plasma. Proteomes. 2019 Apr 25;7(2). pii: E17. doi: 10.3390/proteomes7020017. Askeland G, Rodinova M, Štufková H, Dosoudilova Z, Baxa M, Smatlikova P, Bohuslavova B, Klempir J, Nguyen TD, Kuśnierczyk A, Bjørås M, Klungland A, Hansikova H, Ellederova Z, Eide L. A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies. Dis Model Mech. 2018 Oct 24;11(10). pii: dmm035949. doi: 10.1242/dmm.035949. Askeland G, Dosoudilova Z, Rodinova M, Klempir J, Liskova I, Kuśnierczyk A, Bjørås M, Nesse G, Klungland A, Hansikova H, Eide L. Increased nuclear DNA damage precedes mitochondrial dysfunction in peripheral blood mononuclear cells from Huntington's disease patients. Sci Rep. 2018 Jun 29;8(1):9817. doi: 10.1038/s41598- 018-27985-y. Krizova J, Stufkova H, Rodinova M, Macakova M, Bohuslavova B, Vidinska D, Klima J, Ellederova Z, Pavlok A, Howland DS, Zeman J, Motlik J, Hansikova H. Mitochondrial Metabolism in a Large-Animal Model of Huntington Disease: The Hunt for Biomarkers in the Spermatozoa of Presymptomatic Minipigs. Neurodegener Dis. 2017;17(4-5):213-226. doi: 10.1159/000475467. Epub 2017 Jun 21 Dušek P, Rodinová M, Lišková I, Klempíř J, Zeman J, Roth J, Hansíková H.Buccal Respiratory Chain Complexes I and IV Quantities in Huntington's Disease Patients. Folia Biol (Praha). 2018;64(1):31-34. ID: 322
Mitochondrial mechanisms in neurodegeneration and neurodevelopment The mitochondrial DNA depletion syndrome protein FBXL4 mediates the degradation of the mitophagy receptors BNIP3 and NIX to suppress mitophagy 1School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia; 2Department of Biotechnology, School of Biotechnology, Viet Nam National University-International University, Ho Chi Minh City, Vietnam; 3Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, USA; 4Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, USA; 5The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia; 6Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 8The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia Bibliography
Nguyen-Dien G, Kozul K, Cui Y, Townsend B, Gosavi Kulkarni P, Ooi S, Marzio A, Carrodus N, Zuryn S, Pagano M et al. (2022) FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. bioRxiv 2022.10.12.511867; doi: https://doi.org/10.1101/2022.10.12.511867 ID: 467
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondria released from astrocytes contribute to the striatal neuronal vulnerability in Huntington’s disease 1Departament de Biomedicina, Facultat de Medicina. Universitat de Barcelona, Spain; 2Institut de Neurociències. Universitat de Barcelona, Spain; 3Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; 4Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Bibliography
Cherubini M, Lopez-Molina L, Gines S. Mitochondrial fission in Huntington's disease mouse striatum disrupts ER-mitochondria contacts leading to disturbances in Ca2+ efflux and Reactive Oxygen Species (ROS) homeostasis. Neurobiology of Disease, 2020. IF: 5,22. DOI: 10.1016/j.nbd.2020.104741. ID: 554
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitophagy in CHCHD10 related disorders: beneficial or a deleterious pathway? Institute for Research on Cancer and Aging, Nice (IRCAN) - France ID: 582
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Harlequin mice exhibit cognitive impairment, severe loss of Purkinje cells and a compromised bioenergetic status due to the absence of Apoptosis Inducing Factor 1Université Paris Cité, NeuroDiderot, Inserm, F-75019 Paris, France; 2Neonatal Research Group, Instituto de Investigación Sanitaria La Fe (IISLAFE), Valencia, Spain; 3Department of Physiology, University of Valencia, Vicent Andrés Estellés s/n, 46100 12 Burjassot, Spain; 4Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; 5Université de Paris, UMR-S 1144 Inserm, 75006 Paris, France; 6Université Paris Cité, Platform of Cellular and Molecular Imaging, US25 Inserm, UAR3612 CNRS, 75006 Paris, France Bibliography
1.Hélène Cwerman-Thibault, Christophe Lechauve, Vassilissa Malko-Baverel, Sébastien Augustin, Gwendoline Le Guilloux, Élodie Reboussin, Julie Degardin-Chicaud, Manuel Simonutti, Thomas Debeir, Marisol Corral-Debrinski. Neuroglobin effectively halts vision loss in Harlequin mice at an advanced stage of optic nerve degeneration. Neurobiology of Disease, 2021. doi.org/10.1016/j.nbd.2021.105483. 2.Hélène Cwerman-Thibault, Vassilissa Malko-Baverel, Gwendoline Le Guilloux, Isabel Torres-Cuevas, Iván Millán, Bruno Saubaméa, Edward Ratcliffe, Djmila Mouri, Virginie Mignon, Odile Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski. Harlequin mice exhibit cognitive impairment, severe loss of Purkinje cells and a compromised bioenergetic status due to the absence of Apoptosis Inducing Factor. Brain Pathology (In submission). 3.Hélène Cwerman-Thibault, Vassilissa Malko-Baverel, Gwendoline Le Guilloux, Edward Ratcliffe, Djmila Mouri, Isabel Torres-Cuevas, Ivan Millán, Virginie Mignon, Bruno Saubaméa, Odile Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski. Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior. (In submission) ID: 638
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Mitochondrial dysfunction and calcium dysregulation in COQ8A-Ataxia Purkinje neurons are rescued by CoQ10 treatment 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Université de Strasbourg, France; 2Institut NeuroMyoGene, UMR5310, INSERM U1217, Université Claude Bernard Lyon I Faculté de médecine, Lyon, France; 3Institut de Biologie du Développement de Marseille (IBDM), CNRS, UMR7288, Aix-Marseille Université, Marseille, France. ID: 1556
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Macromolecular crowding: A novel player in mitochondrial physiology and disease 1Radboud University Medical Center, The Netherlands; 2University of Amsterdam, The Netherlands; 3King's College, London, UK; 4University of Twente, The Netherlands; 5Wageningen University, The Netherlands Bibliography
Bulthuis EP, Dieteren CEJ, Bergmans J, Berkhout J, Wagenaars JA, van de Westerlo EMA, Podhumljak E, Hink MA, Hesp LFB, Rosa HS, Malik AN, Lindert MK, Willems PHGM, Gardeniers HJGE, den Otter WK, Adjobo-Hermans MJW, Koopman WJH. Stress-dependent macromolecular crowding in the mitochondrial matrix. EMBO J. 2023 Feb 24:e108533. doi: 10.15252/embj.2021108533. Epub ahead of print. PMID: 36825437. Bulthuis EP, Adjobo-Hermans MJW, Willems PHGM, Koopman WJH. Mitochondrial Morphofunction in Mammalian Cells. Antioxid Redox Signal. 2019 Jun 20;30(18):2066-2109. doi: 10.1089/ars.2018.7534. Epub 2018 Nov 29. Dieteren CE, Gielen SC, Nijtmans LG, Smeitink JA, Swarts HG, Brock R, Willems PH, Koopman WJ. Solute diffusion is hindered in the mitochondrial matrix. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8657-62. doi: 10.1073/pnas.1017581108. Epub 2011 May 9. PMID: 21555543; PMCID: PMC3102363. ID: 1342
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Preserved motor function and striatal innervation despite severe degeneration of dopamine neurons upon mitochondrial dysfunction 1Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne, Germany; 2Medical Research Council Mitochondrial Biology Unit, University of Cambridge, UK; 3Medical Research Council Mitochondrial Biology Unit and Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, UK; 4Department of Neurology, Faculty of Medicine and University Hospital Cologne, Germany; 5Institute of Radiochemistry and Experiment Molecular Imaging, Faculty of Medicine and University Hospital of Cologne, Germany; 6Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Faculty of Medicine and University Hospital Cologne, Germany; 7Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne; Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD) and Center for Molecular Medicine Cologne, University of Cologne, Germany Bibliography
(1) Ricke, K.M., T. Paß, S. Kimoloi, K. Fährmann, C. Jüngst, A. Schauss, O.R. Baris, M. Aradjanski, A. Trifunovic, T.M. Eriksson Faelker, M. Bergami and R.J. Wiesner (2020): Mitochondrial dysfunction combined with high calcium load leads to impaired antioxidant defense underlying the selective loss of nigral dopaminergic neurons. J Neuroscience 40: 1975-1986 (2) Dölle C., Flønes I., Nido G.S., Miletic H., Osuagwu N., Kristoffersen S., Lilleng P.K., Larsen J.P., Tysnes O.B., Haugarvoll K., Bindoff L.A., Tzoulis C. (2016): Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun. 7: 13548. ID: 1320
Mitochondrial mechanisms in neurodegeneration and neurodevelopment The mitochondrial DNA depletion syndrome protein FBXL4 mediates the degradation of the mitophagy receptors BNIP3 and NIX to suppress mitophagy 1School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia; 2Department of Biotechnology, School of Biotechnology, Viet Nam National University-International University, Ho Chi Minh City, Vietnam; 3Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, USA; 4Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, USA; 5The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia; 6Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 8The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia Bibliography
Nguyen-Dien G, Kozul K, Cui Y, Townsend B, Gosavi Kulkarni P, Ooi S, Marzio A, Carrodus N, Zuryn S, Pagano M et al. (2022) FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors. bioRxiv 2022.10.12.511867; doi: https://doi.org/10.1101/2022.10.12.511867 ID: 1329
The impact of mtDNA variation and environment on rare and common diseases Parsing universal heteroplasmy in a large maternal lineage carrying the common LHON variant m.11778G>A/MT-ND4 1Azienda USL di Bologna - IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; 3Istituto Italiano di Tecnologia – IIT, Genova, Italy; 4Instituto de Olhos de Colatina, Colatina, Espírito Santo, Brazil; 5Departamento de Oftalmologia e Ciências Visuais, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; 6Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 7Medical Research Council Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK ID: 1441
The impact of mtDNA variation and environment on rare and common diseases PNPLA3, MBOAT7 and TM6SF2 modify mitochondrial dynamics in NAFLD patients: dissecting the role of cell-free circulating mtDNA and copy number 1Fondazione IRCCS Cà Granda Ospedale Policlinico, Italy; 2Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 3Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy ID: 444
The impact of mtDNA variation and environment on rare and common diseases The overexpression of TM6SF2 and/or MBOAT7 wild-type genes restores the mitochondrial lifecycle and activity in an in vitro NAFLD model 1Fondazione IRCCS Cà Granda Ospedale Policlinico, Italy; 2Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Italy; 3Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy |
| Date: Wednesday, 14/June/2023 | |
| 8:00am - 6:00pm | Slides Center Location: Slides Center |
| 8:00am - 6:00pm | Registration Desk Location: Bologna Congress Center |
| 9:00am - 10:30am | Session 4.1: Therapy 1: preclinical developments Location: Bologna Congress Center - Sala Europa Session Chair: Michal Minczuk Session Chair: Maria Falkenberg Invited Speaker: N. Larsson; C. Viscomi |
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Invited
ID: 603 Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity The Organization of the Respiratory Chain and its role in Metabolism Karolinska Institutet, Sweden Invited
ID: 677 Invited Speakers Developing new therapies for mitochondrial diseases University of Padova, Italy Oral presentation
ID: 193 Therapy 1: preclinical developments AAV-mediated transduction of the nuclear-coded mitochondrial ANT1 gene can ameliorate mouse Ant1-/- pathology: a step toward the treatment of mitochondrial cardiomyopathy 1The Children's Hospital of Philadelphia, PA USA; 2Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA USA Oral presentation
ID: 371 Therapy 1: preclinical developments Preclinical studies of efficacy and genetic safety of deoxyribonucleosides as a therapy for mitochondrial DNA maintenance defects 1Research Group on Neuromuscular and Mitochondrial Diseases, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; 2Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; 3Department of Clinical and Molecular Genetics, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; 4Institut Cochin, INSERM Unité 1016–Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) 8104–Service de Biochimie Métabolique et Centre de Génétique Moléculaire et Chromosomique, Groupement Hospitalier Universitaire (GHU) Pitié-Salpétrière, Assistance Publique–Hôpitaux de Paris (AP–HP)–Université Paris Descartes, Paris, France; 5Mitochondrial and Neuromuscular Disorders Group, '12 de Octubre’ Hospital Research Institute (imas12), Madrid, Spain; 6Pediatric Neurology Department, Badajoz Hospital Complex, Badajoz, Spain; 7Pediatric Neurology Department, Donostia University Hospital, San Sebastian, Spain; 8Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián. Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain; Neurosciences Department, Basque Country University, San Sebastián, Spain; 9Centro de Investigación en Red de Enfermedades Neurodegenerativas, CIBERNED (CIBER), Instituto Carlos III, Madrid, Spain; 10Children Neuromuscular Diseases Unit, Pediatrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; 11Department of Neurology, Neuromuscular Diseases Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain; 12Secció d'Errors Congènits del Metabolisme-IBC, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, IDIBAPS, Barcelona, Spain; 13Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; 14Department of Clinical Movement Neurosciences, Royal Free Campus, University College of London, Queen Square Institute of Neurology, London, UK; 15Neuromuscular Unit, Neurology Department, Sant Joan de Déu Research Institute, Sant Joan de Déu Hospital, Barcelona, Spain; 16Neuropediatra, Neurolinkia & Hospital Viamed Santa Ángela De la Cruz, Sevilla, Spain; 17Neuromuscular Diseases Unit, Neurology Department, Hospital Universitario Virgen del Rocío/ Instituto de Biomedicina de Sevilla, Sevilla, Spain Flash Talk
ID: 152 Therapy 1: preclinical developments The mitoDdCBE system as a mitochondrial gene therapy approach 1University of Miami, United States of America; 2Max Planck Institute of Biochemistry, Germany; 3Broad Institute, Harvard University, and HHMI, United States of America Bibliography
Mitochondrial genome engineering coming-of-age. Barrera-Paez et al. Trends Genet. 2022, May 19. PMID: 35599021. Mitochondrial gene editing. Shoop et al (Barrera-Paez as third author). Nat Rev Methods Primers. 2023, in press (March 16). Flash Talk
ID: 512 Therapy 1: preclinical developments Genetic variants impact on NQO1 expression and activity driving efficacy of idebenone treatment in Leber’s hereditary optic neuropathy cell models 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy.; 3Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 4Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. Flash Talk
ID: 292 Therapy 1: preclinical developments Peptide mimetic molecules as potential therapeutic agents against diseases related to mt-tRNA point mutations. 1Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy; 2Department of Biochemical Sciences "A. Rossi Fanelli, Sapienza University of Rome, Italy; 3Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy Bibliography
Perli E, Pisano A, Pignataro MG, Campese AF, Pelullo M, Genovese I, de Turris V, Ghelli AM, Cerbelli B, Giordano C, Colotti G, Morea V, d'Amati G. Exogenous peptides are able to penetrate human cell and mitochondrial membranes, stabilize mitochondrial tRNA structures, and rescue severe mitochondrial defects. FASEB J. 2020 Jun;34(6):7675-7686. doi: 10.1096/fj.201903270R Italian Patent n.102021000032930 THERAPEUTICAL PEPTIDOMIMETIC Inventors: Giulia d’Amati, Veronica Morea, Annalinda Pisano, Elena Perli, Maria Gemma Pignataro International application No. PCT/IB2022/062354 |
| 10:30am - 10:45am | Coffee Break Location: Bologna Congress Center |
| 10:45am - 12:15pm | Session 4.2: Therapy 2: clinical trials Location: Bologna Congress Center - Sala Europa Session Chair: Caterina Garone Session Chair: Chiara La Morgia |
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Invited
ID: 166 Invited Speakers Clinical trials for Leber hereditary optic neuropathy Emory University School of Medicine, United States of America Bibliography
Newman NJ, Yu-Wai-Man P, Subramanian PS, et al. Bilateral injection of lenadogene nolparvovec for m.11778G>A MT-ND4 Leber hereditary optic neuropathy. Brain 2023;awac421.doi: 10.1093/brain/awac421. Carelli V, Newman NJ, Yu-Wai-Man P, et al. Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in Leber hereditary optic neuropathy patients carrying the m.11778G>A MT-ND4 mutation. Ophthalmol Ther, 2022, https://doi.org/10.007/s40123-022-0061-x . Newman NJ, Yu-Wai-Man P, Biousse V. Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management. Lancet Neurol 2023;S1474-4422(22)00174-0. doi: 10.1016/S1474-4422(22)00174-0. Sahel JA, Newman NJ, Yu-Wai-Man P, Vignal-Clermont C, Carelli V, Biousse V, Moster ML, Sergott R, Klopstock T, Sadun AA, Blouin L, Katz B, Taiel M. Gene therapies for the treatment of Leber hereditary optic neuropathy. Int Ophthalmol Clin 61:195-208 2021. Newman NJ, Yu-Wai-Man P, Carelli V, et al, for the LHON Study Group. Efficacy and safety of intravitreal gene therapy for Leber hereditary optic neuropathy treated within 6 months of disease onset. Ophthalmology 128:649-660, 2021. Yu-Wai-Man P, Newman NJ, Carelli V, et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med 2020 Dec 9;12(573):eaaz7423. Catarino C, von Livonious B, Gallenmuller C, Banik R, Matloob S, Tamhankar M, Castillo Campillo LC, Dahlgren N, Friedburg C, Halfpenny C, Lincoln J, Traber G, Acaroglu G, Black G, Doncel C, Fraser C, Jakubaszko J, Landau K, Langenegger S, Munoz Negrete F, Newman N, Poulton J, Scoppettuolo E, Subramanian P, Toosy A, Vidal M, Vincent A, Votruba M, Zarowski M, Zermansky A, Lob F, Rudolph G, Mikazans O, Silva M, Lloria X, Metz G, Klopstock T. Real world clinical experience with idebenone in the treatment of Leber’s hereditary optic neuropathy. J Neuro-ophthalmol 40: 558–565, 2020. Invited
ID: 2104 Invited Speakers Development of deoxynucleoside therapy for mitochondrial DNA depletion/deletions syndrome 1Columbia University Irving Medical Center, New York, USA, United States of America; 2University of Bologna, Bologna, Italy; 3Univerity of Malaga, Malaga, Spain; 4University Hospital, 12 de Octubre, Madrid, Spain; 5Vall d’Hebron Institut de Recerca, Barcelona, Spain Bibliography
1.Lopez-Gomez C, Camara Y, Hirano M, Marti R, nd EWP. 232nd ENMC international workshop: Recommendations for treatment of mitochondrial DNA maintenance disorders. 16 - 18 June 2017, Heemskerk, The Netherlands. Neuromuscul Disord. 2022;32(7):609-20. Epub 20220514. doi: 10.1016/j.nmd.2022.05.008. PubMed PMID: 35641351. 2.Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001;29(3):342-4. PubMed PMID: 11687801. 3.Garone C, Taylor RW, Nascimento A, Poulton J, Fratter C, Dominguez-Gonzalez C, Evans JC, Loos M, Isohanni P, Suomalainen A, Ram D, Hughes MI, McFarland R, Barca E, Lopez Gomez C, Jayawant S, Thomas ND, Manzur AY, Kleinsteuber K, Martin MA, Kerr T, Gorman GS, Sommerville EW, Chinnery PF, Hofer M, Karch C, Ralph J, Camara Y, Madruga-Garrido M, Dominguez-Carral J, Ortez C, Emperador S, Montoya J, Chakrapani A, Kriger JF, Schoenaker R, Levin B, Thompson JLP, Long Y, Rahman S, Donati MA, DiMauro S, Hirano M. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-21. Epub 20180330. doi: 10.1136/jmedgenet-2017-105012. PubMed PMID: 29602790; PMCID: PMC6073909. 4.Wang J, Kim E, Dai H, Stefans V, Vogel H, Al Jasmi F, Schrier Vergano SA, Castro D, Bernes S, Bhambhani V, Long C, El-Hattab AW, Wong LJ. Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect. Mol Genet Metab. 2018;124(2):124-30. Epub 20180428. doi: 10.1016/j.ymgme.2018.04.012. PubMed PMID: 29735374. 5.Hidago-Gutierrez A, Shintaku J, Barriocanal-Casado E, Saneto R, Ramon J, Garrabou G, Tort F, Millsenda JC, Gort L, Pesini A, Tadesse S, King M-C, Martí R, Ribes A, Hirano M, editors. Guanylate Kinase 1 Deficiency: A Novel and Potentially Treatable Form of Mitochondrial DNA Depletion/Deletions Syndrome. Euromit 2023; 2023; Bologna, Italy. 6.Akman HO, Dorado B, Lopez LC, Garcia-Cazorla A, Vila MR, Tanabe LM, Dauer WT, Bonilla E, Tanji K, Hirano M. Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance. Hum Mol Genet. 2008;17(16):2433-40. Epub 20080508. doi: 10.1093/hmg/ddn143. PubMed PMID: 18467430; PMCID: PMC3115590. 7.Zhou X, Solaroli N, Bjerke M, Stewart JB, Rozell B, Johansson M, Karlsson A. Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice. Hum Mol Genet. 2008;17(15):2329-35. Epub 20080422. doi: 10.1093/hmg/ddn133. PubMed PMID: 18434326. 8.Blazquez-Bermejo C, Molina-Granada D, Vila-Julia F, Jimenez-Heis D, Zhou X, Torres-Torronteras J, Karlsson A, Marti R, Camara Y. Age-related metabolic changes limit efficacy of deoxynucleoside-based therapy in thymidine kinase 2-deficient mice. EBioMedicine. 2019;46:342-55. Epub 20190724. doi: 10.1016/j.ebiom.2019.07.042. PubMed PMID: 31351931; PMCID: PMC6711114. 9.Garone C, Garcia-Diaz B, Emmanuele V, Lopez LC, Tadesse S, Akman HO, Tanji K, Quinzii CM, Hirano M. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. EMBO Mol Med. 2014;6(8):1016-27. doi: 10.15252/emmm.201404092. PubMed PMID: 24968719; PMCID: PMC4154130. 10.Lopez-Gomez C, Levy RJ, Sanchez-Quintero MJ, Juanola-Falgarona M, Barca E, Garcia-Diaz B, Tadesse S, Garone C, Hirano M. Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency. Ann Neurol. 2017;81(5):641-52. doi: 10.1002/ana.24922. PubMed PMID: 28318037. 11.Lopez-Gomez C, Sanchez-Quintero MJ, Lee EJ, Kleiner G, Tadesse S, Xie J, Akman HO, Gao G, Hirano M. Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency. Ann Neurol. 2021;90(4):640-52. Epub 20210813. doi: 10.1002/ana.26185. PubMed PMID: 34338329; PMCID: PMC9307066. 12.Dominguez-Gonzalez C, Madruga-Garrido M, Mavillard F, Garone C, Aguirre-Rodriguez FJ, Donati MA, Kleinsteuber K, Marti I, Martin-Hernandez E, Morealejo-Aycinena JP, Munell F, Nascimento A, Kalko SG, Sardina MD, Alvarez Del Vayo C, Serrano O, Long Y, Tu Y, Levin B, Thompson JLP, Engelstad K, Uddin J, Torres-Torronteras J, Jimenez-Mallebrera C, Marti R, Paradas C, Hirano M. Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy. Ann Neurol. 2019;86(2):293-303. Epub 20190617. doi: 10.1002/ana.25506. PubMed PMID: 31125140; PMCID: PMC7586249. Oral presentation
ID: 110 Therapy 2: clinical trials Histopathological and molecular characterization in ocular post-mortem analyses following AAV2 gene therapy for LHON 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 3IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 4Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 5Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 6Charles River Laboratories, Evreux, France; 7Gensight Biologics, Paris, France Bibliography
Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernández G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; theLHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2022 Nov 30. doi: 10.1007/s40123-022-00611-x. Epub ahead of print. PMID: 36449262. Newman NJ, Schniederjan M, Mendoza PR, Calkins DJ, Yu-Wai-Man P, Biousse V, Carelli V, Taiel M, Rugiero F, Singh P, Rogue A, Sahel JA, Ancian P. Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report. BMC Neurol. 2022 Jul 12;22(1):257. doi: 10.1186/s12883-022-02787-y. PMID: 35820885; PMCID: PMC9277876. Calkins DJ, Yu-Wai-Man P, Newman NJ, Taiel M, Singh P, Chalmey C, Rogue A, Carelli V, Ancian P, Sahel JA. Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates. Mol Ther Methods Clin Dev. 2021 Oct 1;23:307-318. doi: 10.1016/j.omtm.2021.09.013. PMID: 34729378; PMCID: PMC8526752. Oral presentation
ID: 546 Therapy 2: clinical trials Combatting myopathy in m.3243A>G mutation carriers: first in human transplantation of autologous mesoangioblasts 1Department of Toxicogenomics, Maastricht University Medical Centre+, Maastricht, The Netherlands; 2School for Mental Health and Neurosciences (MHeNS), Maastricht University Medical Centre+, Maastricht, The Netherlands; 3Department of Neurology, Maastricht University Medical Centre+, Maastricht, The Netherlands; 4Department of Radiology, Maastricht University Medical Centre+, Maastricht, The Netherlands; 5School for Developmental Biology and Oncology (GROW), Maastricht University Medical Centre+, Maastricht, The Netherlands; 6Center for Cell and Gene Therapy (CCG), Leiden University Medical Center, Leiden, The Netherlands; 7Department of Rehabilitation Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; 8SMRC – Sports Medicine Research Center, BIOMED - Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; 9Neuromuscular and Mitochondrial research center (NeMo), Rotterdam/Maastricht, The Netherlands Flash Talk
ID: 573 Therapy 2: clinical trials PHEMI: Phenylbutyrate Therapy in Mitochondrial Diseases with lactic acidosis: an open label clinical trial in MELAS and PDH deficiency patients. 1Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Experimental Neuroscience, Unit of Medical Genetics and Neurogenetics, Milan, Italy; 2Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Pediatric Neurosciences, Milan, Italy; 3Neurological Institute, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Bibliography
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986. PMID: 23467562 Flash Talk
ID: 355 Therapy 2: clinical trials Niacin treatment improves metabolic changes in early-stage mitochondrial myopathy 1Research Program for Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 3Department of Neurosciences, Helsinki University Hospital, Helsinki, Finland; 4Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospital, Helsinki, Finland; 5HUS Diagnostic Center, Radiology, Helsinki University and Helsinki University Hospital, Helsinki, Finland; 6Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; 7Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 8Healthy Weight Hub, Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 9Helsinki University Hospital Diagnostic Centre, Helsinki, Finland Bibliography
Eija Pirinen, Mari Auranen, Nahid A. Khan, Virginia Brilhante, Niina Urho, Alberto Pessia, Antti Hakkarainen, Juho Kuula, Ulla Heinonen, Mark S. Schmidt, Kimmo Haimilahti, Päivi Piirilä, Nina Lundbom, Marja-Riitta Taskinen, Charles Brenner, Vidya Velagapudi, Kirsi H. Pietiläinen, Anu Suomalainen. Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab 2020;31(6):1078-1090.e5. Flash Talk
ID: 102 Therapy 2: clinical trials Use of lenadogene nolparvovec gene therapy for Leber hereditary optic neuropathy in early access programs 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 3Centre Hospitalier National d’Ophtalmologie des Quinze Vingts, Paris, France; 4Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 5Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 6Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 7Institut de Génétique Médicale d’Alsace, CHU de Strasbourg, Strasbourg, France; 8Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University, Munich, Germany; 9University Hospital, Ludwig-Maximilians-University, Munich, Germany; 10Service Explorations de la Vision et Neuro-Ophtalmologie, CHU de Lille, Lille, France; 11Service d'Ophtalmologie, CHU de Rennes, Rennes, France; 12Service d'Ophtalmologie, CHU de Bordeaux, Groupe Hospitalier Pellegrin, Bordeaux, France; 13Service d'Ophtalmologie, CHU de Nantes, Nantes, France; 14Service de Neuro-Cognition et Neuro-Ophtalmologie, CHU de Lyon, Lyon, France; 15Service d'Ophtalmologie, Centre Hospitalier de Valence, Valence, France; 16Service d'Ophtalmologie, CHU de Caen, Caen, France; 17Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA; 18Retina Consultants, P.C, Hartford, Connecticut, USA; 19Service d'Ophtalmologie, Hôpital Ophtalmique Jules-Gonin, Lausanne, Switzerland; 20Centre Hospitalier de Wallonie Picarde, Tournai, Belgium; 21GenSight Biologics, Paris, France; 22Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; 23Department of Biomedical and Neuromotor Sciences, DIBINEM, Bologna, Italy Bibliography
Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, La Morgia C, Karanjia R, Taiel M, Blouin L, Burguière P, Smits G, Chevalier C, Masonson H, Salermo Y, Katz B, Picaud S, Calkins DJ, Sahel JA. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med. 2020 Dec 9;12(573):eaaz7423. doi: 10.1126/scitranslmed.aaz7423. PMID: 33298565. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. PMID: 34108929; PMCID: PMC8181419. Biousse V, Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Esposti S, La Morgia C, Priglinger C, Karanja R, Blouin L, Taiel M, Sahel JA; LHON Study Group. Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study. J Neuroophthalmol. 2021 Sep 1;41(3):309-315. doi: 10.1097/WNO.0000000000001367. PMID: 34415265; PMCID: PMC8366761. |
| 12:15pm - 1:05pm | Industry Workshop: Pretzel Therapeutics Location: Bologna Congress Center - Sala Europa |
| 12:15pm - 1:15pm | Lunch Location: Bologna Congress Center - Sala Europa |
| 1:15pm - 2:45pm | Session 4.3: Therapy 3: reproductive options and mtDNA editing Location: Bologna Congress Center - Sala Europa Session Chair: Carlo Viscomi Session Chair: Daniela Zuccarello Invited Speaker: M. Herbert; M. Minczuk |
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ID: 2109 Invited Speakers Mitochondrial replacement in action 1Newcastle University, United Kingdom; 2Newcastle Fertility Centre Bibliography
N. Costa-Borges et al., First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility. Fertil Steril, S0015-0282(23)00136-X (2023). Invited
ID: 2108 Invited Speakers The therapeutic potential of mitochondrial genome engineering MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK Bibliography
Michal Minczuk is a MRC Investigator at the MRC Mitochondrial Biology Unit (MBU) at University of Cambridge, leading a research programme in mitochondrial genetics. His programme encompasses the development of methods for controlled editing of the mammalian mitochondrial genome, mechanistic studies of mitochondrial gene maintenance and expression in health and disease, and the development of advanced gene therapies for mtDNA dysfunction. Oral presentation
ID: 160 Therapy 3: reproductive options and mtDNA editing MitoKO: A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK Bibliography
Silva-Pinheiro, P., Mutti, C.D., Van Haute, L. et al. A library of base editors for the precise ablation of all protein-coding genes in the mouse mitochondrial genome. Nat. Biomed. Eng (2022). https://doi.org/10.1038/s41551-022-00968-1 Silva-Pinheiro, P., Nash, P.A., Van Haute, L. et al. In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue. Nat Commun 13, 750 (2022). https://doi.org/10.1038/s41467-022-28358-w Silva-Pinheiro, P., Minczuk, M. The potential of mitochondrial genome engineering. Nat Rev Genet 23, 199–214 (2022). https://doi.org/10.1038/s41576-021-00432-x Oral presentation
ID: 174 Therapy 3: reproductive options and mtDNA editing Risk of mtDNA reversal among children born after mitochondrial replacement therapy 1Oregon Health & Science University, United States of America; 2Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, United States of America Bibliography
First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility. Fertility and Sterility, 2023 Flash Talk
ID: 155 Therapy 3: reproductive options and mtDNA editing Specific elimination of m.3243A>G mutant mitochondria DNA using mitoARCUS 1Precision BioSciences - Durham, NC, United States of America; 2University of Miami - Miami, FL, United States of America Bibliography
Shoop WK, Gorsuch CL, Bacman SR, Moraes CT. Precise and simultaneous quantification of mitochondrial DNA heteroplasmy and copy number by digital PCR. J Biol Chem. 2022;298(11):102574. doi:10.1016/j.jbc.2022.102574 Flash Talk
ID: 453 Therapy 3: reproductive options and mtDNA editing MitoCRISPR/Cas9 shifts mtDNA heteroplasmy not as effective as other site-specific nucleases. 1Novosibirsk State University, Novosibirsk, Russia; 2Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; 3Skolkovo Institute of Science and Technology, Moscow, Russia Bibliography
1.Tanaka, M.; Borgeld, H.-J.; Zhang, J.; Muramatsu, S.; Gong, J.-S.; Yoneda, M.; Maruyama, W.; Naoi, M.; Ibi, T.; Sahashi, K.; et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J. Biomed. Sci. 2002, 9, 534–41. https://doi.org/10.1159/000064726. 2. Zakirova, E.G.; Vyatkin, Y.V.; Verechshagina, N.A.; Muzyka, V.V.; Mazunin, I.O.; Orishchenko, K.E. Study of the effect of the introduction of mitochondrial import determinants into the gRNA structure on the activity of the gRNA/SpCas9 complex in vitro.Vavilov Journal of Genetics and Breeding 2020, 24(5):512-518. https://doi.org/10.18699/VJ20.643. 3.Silva-Pinheiro, P., Minczuk, M. The potential of mitochondrial genome engineering. Nat Rev Genet 23, 199–214 (2022). https://doi.org/10.1038/s41576-021-00432-x. 4. Zakirova, E.G.; Muzyka, V.V.; Mazunin, I.O.; Orishchenko, K.E. Natural and Artificial Mechanisms of Mitochondrial Genome Elimination. Life 2021, 11, 76. https://doi.org/10.3390/life11020076. Flash Talk
ID: 271 Therapy 3: reproductive options and mtDNA editing Prenatal diagnostics for a family with 13513G>A mtDNA mutation associated with Leigh Syndrome 1Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, United States of America; 2Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health and Science University, United States of America |
| 2:45pm - 4:15pm | Tea Break and poster session Location: Bologna Congress Center Session topics: - Late Breaking News - mtDNA maintenance and expression - Therapy 1: preclinical developments - Therapy 2: clinical trials |
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ID: 694
Late breaking news Precision Medicine Applied to Leigh Syndrome: development of an In Utero fetal gene therapy approach 1Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy; 2Fetal Medicine and Surgery Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.; 3Department of Biomedical Sciences, University of Padova, Italy; 4Department of Neurosciences, University of Padova, Italy; 5Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona, Italy; 6Department of Medical Biotechnology and Translational Medicine, University of Milan, Italy ID: 684
Late breaking news AAV-based liver-targeted gene therapy for MNGIE: proposal for a clinical trial 1MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK; 2Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK; 3Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, and Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Catalonia ID: 690
Late breaking news Experimental model for studying clinical variability of Thymidine Kinase 2 deficiency with induced pluripotent stem cells 1Alma Mater Studiorum University of Bologna, Department of Medical and Surgical Sciences, Bologna, Italy; 2Alma Mater Studiorum University of Bologna, University of Bologna, Department of Pharmacy and Biotechnology, Bologna, Italy; 3IRCCS Istituto delle Scienze Neurologiche, Programma di Neurogenetica, Bologna, Italy; 4IRCCS Istituto delle Scienze Neurologiche, UOC Neuropsichiatia dell'età pediatrica, Bologna, Italy ID: 692
Late breaking news Mitochondrial genome variability in COVID-19 patients 1Azienda USL di Bologna - IRCCS Istituto delle scienze Neurologiche di Bologna, Italy, Italy; 2Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, BO, Italy; 3Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 4Unit of Infectious Diseases and Clinical Microbiology, University Hospital Virgen Macarena, Institute of Biomedicine of Seville (IBIS)/CSIC, Seville, Spain; 5Medical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 6Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy ID: 691
Late breaking news Decoding the role of optic atrophy1 (OPA1) non-synonymous single nucleotide polymorphisms in mitochondrial DNA maintenance defects Jawaharlal Nehru Centre for Advanced Scientific Research, India Bibliography
1.Gavin Hudson, Patrizia Amati-Bonneau, Emma L. Blakely, Joanna D. Stewart, Langping He, Andrew M. Schaefer, Philip G. Griffiths, Kati Ahlqvist, Anu Suomalainen, Pascal Reynier, Robert McFarland, Douglass M. Turnbull, Patrick F. Chinnery, Robert W. Taylor, Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance, Brain, Volume 131, Issue 2, February 2008, Pages 329–337, https://doi.org/10.1093/brain/awm272 2.Ayman W. El-Hattab, William J. Craigen, Fernando Scaglia, Mitochondrial DNA maintenance defects, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1863, Issue 6, 2017, Pages 1539-1555, ISSN 0925-4439, https://doi.org/10.1016/j.bbadis.2017.02.017. ID: 688
Late breaking news Feasibility, safety, and efficacy of Ketogenic Diet in patients with mitochondrial myopathy 1Department of Gastroenterology and Hepatology-Dietetics, Radboudumc, Nijmegen, The Netherlands; 2Radboud Centre for Mitochondrial Medicine (RCMM) , Nijmegen, The Netherlands; 3Department of Physiology, Radboudumc, Nijmegen, The Netherlands; 4Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands; 5University Children’s Hospital, Paracelsus Medical University, Salzburg, Austria; 6Human and Animal Physiology, Wageningen University, The Netherlands; 7Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands Bibliography
1. Ketogenic diet for mitochondrial disease: a systematic review on efficacy and safety. Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB. Orphanet J Rare Dis. 2021 Jul 3;16(1):295. ID: 266
mtDNA maintenance and expression Degrading factors of mitoribosome quality control and their mitigation of translation-induced stress 1Wellcome Centre for Mitochondrial Research, United Kingdom; 2University of Helsinki ID: 530
mtDNA maintenance and expression Mitochondrial DNA Double-Strand Breaks lead to the formation of mtDNA deletions which are increased by MgmeI knockout in vivo. University of Miami, United States of America Bibliography
•ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly. Arguello T, Peralta S, Antonicka H, Gaidosh G, Diaz F, Tu YT, Garcia S, Shiekhattar R, Barrientos A, Moraes CT. Cell Rep. (2021) Dec 21;37(12):110139. •Metformin delays neurological symptom onset in a mouse model of neuronal complex I deficiency. Peralta S, Pinto M, Arguello T, Garcia S, Diaz F, Moraes CT. (2020) JCI Insight. Nov 5;5(21):141183 •Myopathy reversion in mice after restauration of mitochondrial complex I. Pereira CV, Peralta S, Arguello T, Bacman SR, Diaz F, Moraes CT. (2020). EMBO Mol Med. Jan 9:e10674. ID: 234
mtDNA maintenance and expression Mutating the binding interphases of SLIRP and LRPPRC uncover specific roles for these proteins in optimizing mitochondrial translation. 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Lund University, Lund 223 87, Sweden Bibliography
Diana Rubalcava-Gracia, Rodolfo García-Villegas, Nils-Göran Larsson. No role for nuclear transcription regulators in mammalian mitochondria? Molecular Cell, 2022. PMID: 36182692. ID: 145
mtDNA maintenance and expression A disease-causing mutation (p.F907I) reveals a novel pathogenic mechanism for POLG-related diseases. 1University of Gothenburg, Sweden; 2Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; 3Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden Bibliography
1. TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study. Percetti M, Franco G, Monfrini E, Caporali L, Minardi R, La Morgia C, Valentino ML, Liguori R, Palmieri I, Ottaviani D, Vizziello M, Ronchi D, Di Berardino F, Cocco A, Macao B, Falkenberg M, Comi GP, Albanese A, Giometto B, Valente EM, Carelli V, Di Fonzo A. Mov Disord. 2022 Sep;37(9):1938-1943. doi: 10.1002/mds.29139. 2. The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication. Jiang M, Xie X, Zhu X, Jiang S, Milenkovic D, Misic J, Shi Y, Tandukar N, Li X, Atanassov I, Jenninger L, Hoberg E, Albarran-Gutierrez S, Szilagyi Z, Macao B, Siira SJ, Carelli V, Griffith JD, Gustafsson CM, Nicholls TJ, Filipovska A, Larsson NG, Falkenberg M. Sci Adv. 2021 Jul 2;7(27):eabf8631. doi: 10.1126/sciadv.abf8631. 3.DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion. Silva-Pinheiro P, Pardo-Hernández C, Reyes A, Tilokani L, Mishra A, Cerutti R, Li S, Rozsivalova DH, Valenzuela S, Dogan SA, Peter B, Fernández-Silva P, Trifunovic A, Prudent J, Minczuk M, Bindoff L, Macao B, Zeviani M, Falkenberg M, Viscomi C. Nucleic Acids Res. 2021 May 21;49(9):5230-5248. doi: 10.1093/nar/gkab282. ID: 621
mtDNA maintenance and expression Mitoribosome intrinsic GTPase mS29 acts as a non-canonical molecular switch to facilitate mitochondrial translation 1University of Miami, United States of America; 2Stockholm University, Sweden ID: 443
mtDNA maintenance and expression Nucleoside supplementation in a zebrafish model of RRM2B mitochondrial DNA depletion syndrome alleviates disease associated symptoms. Department of Clinical Neurosciences, University of Cambridge, United Kingdom Bibliography
Van Haute, L., O’Connor, E., Díaz-Maldonado, H., Munro, B. et al. TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease. Nat Commun 14, 1009 (2023). https://doi.org/10.1038/s41467-023-36277-7 Benjamin Munro, Rita Horvath, Juliane S Müller, Nucleoside supplementation modulates mitochondrial DNA copy number in the dguok −/− zebrafish, Human Molecular Genetics, Volume 28, Issue 5, 1 March 2019, Pages 796–803, https://doi.org/10.1093/hmg/ddy389 ID: 335
mtDNA maintenance and expression Non-stop mRNAs generate a ground state of mitochondrial gene expression noise Institute of Biotechnolgy, University of Helsinki, Finland Bibliography
K.Y. Ng, G. Lutfullahoglu Bal, U. Richter, O. Safronov, L. Paulin, C.D. Dunn, V. Paavilainen, Julie Richer, W.G. Newman, R.W. Taylor, B.J. Battersby. (2022). Non-stop mRNAs generate the ground state of mitochondrial gene expression noise. Science Advances. 8(46). ID: 370
mtDNA maintenance and expression Biochemical characterisation of pathological TOP3A variants associated with adult-onset mitochondrial disease 1Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden; 2Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne; 3Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne; 4Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne; 5The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; 6North East and Yorkshire Genomic Laboratory Hub, Central Lab, St. James's University Hospital, Leeds, UK.; 7Leeds Institute of Medical Research, University of Leeds, St. James's University Hospital, Leeds, UK.; 8Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; 9NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne; 10Nuffield Department of Women’s & Reproductive Health, The Women's Centre, University of Oxford, Oxford, UK.; 11Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London; 12Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; 13Department of Internal Medicine, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil.; 14Graduate Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul - Porto Alegre, Brazil.; 15Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, USA; 16Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.; 17The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.; 18The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel; 19The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.; 20Genomics Unit, The Center for Cancer Research, Sheba Medical Center, Israel.; 21Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.; 22Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden. ID: 222
mtDNA maintenance and expression How hot can mitochondria be? Incubation at temperatures above 43 ºC induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria 1Department of Biochemistry and Molecualr and Cellular Biology, Universidad de Zaragoza, Spain; 2Institute for Biocomputation and Physics of Complex Systems (BIFI), Zaragoza, Spain; 3Peaches Biotech Group, Madrid, Spain; 4Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; 5Centro de Investigaciones Biomédicas en Red en Fragilidad y Envejecimiento Saludable, Madrid, Spain Bibliography
1.- Moreno-Loshuertos, R., Marco-Brualla, J., Meade, P., Soler-Agesta, R., Enriquez, J. A., & Fernández-Silva, P. (2023). How hot can mitochondria be? Incubation at temperatures above 43 °C induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria. Mitochondrion, 69, 83–94. Advance online publication. https://doi.org/10.1016/j.mito.2023.02.002 ID: 178
mtDNA maintenance and expression Inhibition of mitochondrial protein Synthesis induces Biosynthesis of oxidative phosphorylation Complex V University College London, United Kingdom ID: 180
mtDNA maintenance and expression Linear DNA driven recombination in human mitochondria. 1University of Eastern Finland, Finland; 2King Abdullah University of Science and Technology (KAUST); 3University of Miami Miller School of Medicine; 4University of North Carolina at Chapel Hill ID: 318
mtDNA maintenance and expression Mitochondrial Topoisomerase 1 in ribonucleotide removal and mtDNA stability Umeå University, Sweden ID: 279
mtDNA maintenance and expression The (in)fidelity of human mitochondrial gene expression University of Helsinki, Finland Bibliography
PEER-REVIEWED PUBLICATIONS (*** corresponding authorship) Tomoda, E., A. Nagao, Y. Shirai, T. Suzuki, B.J. BATTERSBY, T. Suzuki. 2023. Restoration of mitochondrial function through activation of hypomodified tRNAs with pathogenic mutations associated with mitochondrial diseases. Nucleic Acids Research. In press Jett, K. A., Z.N. Baker, A. Hossain, A. Boulet, P.A. Cobine, S. Ghosh, P. Ng, O. Yilmaz, K. Barreto, J. DeCoteau, K. Mochoruk, G.N. Ioannou, C. Savard, S. Yuan, C. Lowden, B.E. Kim, H.Y.M. Cheng, B.J. BATTERSBY, Gohil, V. M., & Leary, S. C. 2023. Mitochondrial dysfunction triggers secretion of the immunosuppressive factor α-fetoprotein. Journal of Clinical Investigation. 133:e154684 Ng, K.Y., G. Lutfullahoglu Bal, U. Richter, O. Safronov, L. Paulin, C.D. Dunn, V.O. Paavilainen, J. Richer, W.G. Newman, R.W. Taylor and B.J. BATTERSBY***. 2022. Non-stop mRNAs generate a ground state of mitochondrial gene expression noise. Science Advances. 8:eabq5234 Ng, K.Y. and B.J. BATTERSBY***. 2022. Sucrose gradient analysis of human mitochondrial ribosomes and RNA. Methods in Molecular Biology. In press. Ng, K.Y., U. Richter, C.B. Jackson, S. Seneca, and B.J. BATTERSBY ***. 2022. Translation of MT-ATP6 pathogenic variants reveals distinct regulatory consequences from the co-translational quality control of mitochondrial protein synthesis. Human Molecular Genetics. 31:1230-1241 Hochberg, I., L.A.M. Demain, J. Richer, K. Thompson, J.E. Urquhart, A. Rea, W. Pagarkar, A. Rodríguez-Palmero, A. Schlüter, E. Verdura, A. Pujol, P. Quijada-Fraile, A. Amberger, A.J. Deutschmann, S. Demetz, M. Gillespie, I.A. Belyantseva, H.J. McMillan, M. Barzik, G.M. Beaman, R. Motha, K.Y. Ng, J. O’Sullivan, S.G. Williams, S.S. Bhaskar, I.R. Lawrence, E.M. Jenkinson, J.L. Zambonin, Z. Blumenfeld, S. Yalonetsky, S. Oerum, W. Rossmanith, Genomics England Research Consortium, W.W. Yue, J. Zschocke, K.J. Munro, B.J. BATTERSBY, T.B. Friedman, R.W. Taylor, R.T. O’Keefe, W.G. Newman. 2021. Biallelic Variants in the Mitochondrial RNase P Subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations. American Journal of Human Genetics. 108: 2195-2204 Itoh, Y., J. Andréll, A. Choi, U. Richter, P. Maiti, A. Barrientos, B.J. BATTERSBY***, A. Amunts. 2021. Mechanism of membrane-tethered mitochondrial protein synthesis. Science. 371:846-849. Gorski, K., A. Spoljaric, T. Nyman, K. Kaila, B.J. BATTERSBY, A.E. Lehesjoki. 2020. Quantitative changes in the mitochondrial proteome of cerebellar synaptosomes from preclinical cystatin B-deficient mice. Frontiers in Molecular Neuroscience. 13:570640. BATTERSBY, B.J.***, U. Richter, and O. Safronov. 2019. Mitochondrial nascent chain quality control determines organelle form and function. ACS Chemical Biology. 14:2396-2405. Forsström, S., C.B. Jackson, C.J. Carroll, M. Kuronen, E. Pirinen, S Pradhan, A. Marmyleva, M. Auranen, I.M. Kleine, N.A. Khan, A. Roivainen, P. Marjamäki, H. Liljenbäck, L. Wang, B.J. BATTERSBY, U. Richter, V. Velagapudi, J. Nikkanen, L. Euro, A. Suomalainen. 2019. Fibroblast growth factor 21 drives dynamics of local and systemic stress responses in mitochondrial myopathy with mtDNA deletions. Cell Metabolism. 30:1040-1054. Richter U., K.Y. Ng, F. Suomi, P. Marttinen, T. Turunen, C. Jackson, A. Suomalainen, H. Vihinen, E. Jokitalo, T.A. Nyman, M.A. Isokallio, J.B. Stewart, C. Mancini, A. Brusco, S. Seneca, A. Lombès, R.W. Taylor, B.J. BATTERSBY***. 2019. Mitochondrial stress response triggered by defects in protein synthesis quality control. Life Science Alliance. 2:e201800219. Mancini, C., E. Hoxha, L. Iommarini, A. Brussino, U. Richter, F. Montarolo, C. Cagnoli, R. Parolisi, D.I.G. Morosini, V. Nicolò, F. Maltecca, L. Muratori, G. Ronchi, S. Geuna, F. Arnaboldi, E. Donetti, E. Giorgio, S. Cavalieri, E. Di Gregorio, E. Pozzi, M. Ferrero, E. Riberi, G. Casari, F. Altruda, E. Turco, G. Gasparre, B.J. BATTERSBY, A.M. Porcelli, E. Ferrero, A. Brusco, F. Tempia. 2019. Mice harbouring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity. Neurobiology of Disease. 124:14-28. Jackson, C.B., M. Huemer, R. Bolognini, F. Martin, G. Szinnai, B.C. Donner, U. Richter, B.J. BATTERSBY, J.M. Nuoffer, A. Suomalainen, A. Schaller. 2019. Mutations in MRPS14 (uS14m) cause perinatal hypertrophic cardiomyopathy with neonatal lactic acidosis, growth retardation, dysmorphic features and neurological involvement. Human Molecular Genetics. 28:639-649. Richter, U., M.E. Evans, W.C. Clark, P. Marttinen, E.A. Shoubridge, A. Suomalainen, A. Wredenberg, A. Wedell, T. Pan, and B.J. BATTERSBY***. 2018. RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis. Nature Communications. 9:3966. Suomalainen, A. and B.J. BATTERSBY***. 2018. Mitochondrial diseases: contribution of organelle stress responses to pathology. Nature Reviews Molecular Cell Biology. 19: 77-92. Thompson, K., N. Mai, M. Oláhová, F. Scialó, L.E. Formosa, D.A. Stroud, M. Garrett, N.Z. Lax, F.M. Robertson, C. Jou, A. Nascimento, C. Ortez, C. Jimenez-Mallebrera, S.A. Hardy, L. He, G.K. Brown, P. Marttinen, R. McFarland, A. Sanz, B.J. BATTERSBY, P.E. Bonnen, M.T. Ryan, Z.M.A. Chrzanowska-Lightowlers, R.N. Lightowlers, and R.W. Taylor. 2018. OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect. EMBO Molecular Medicine. 10:e9060 ID: 525
mtDNA maintenance and expression The role of mitochondrial RNA polymerase in mtDNA replication priming University of Eastern Finland, Finland ID: 308
mtDNA maintenance and expression Mitochondrial content is significantly reduced during the early stages of human pluripotent stem cell differentiation University of Helsinki, Finland Bibliography
# DÖHLA J & KUULUVAINEN E, GEBERT N, AMARAL A, ENGLUND JI, GOPALAKRISHNAN S, KONOVALOVA S, NIEMINEN AI, SALMINEN ES, TORREGROSA-MUÑUMER R, AHLQVIST K, YANG Y, BUI H, OTONKOSKI T, KÄKELÄ R, HIETAKANGAS V, TYYNISMAA H, ORI A & KATAJISTO P. (2022). Metabolic determination of cell fate through selective inheritance of mitochondria. Nature Cell Biol. # TORREGROSA-MUÑUMER R & KENVIN S, REIDELBACH M, PENNONEN P, TURKIA JJ, RANNILA E, KVIST J, SAINIO MT, HUBER N, HERUKKA SK, HAAPASALO A, AURANEN M, TROKOVIC R, SHARMA V, YLIKALLIO E, TYYNISMAA H. (2021). Threshold of heteroplasmic truncating MT-ATP6 mutation in reprogramming, Notch hyperactivation and motor neuron metabolism. Human Molecular Genetics. # TORREGROSA-MUÑUMER R, HANGAS A, GOFFART S, BLEI D, ZSURKA G, GRIFFITH J, KUNZ WS &POHJOISMÄKI J. (2019). Replication fork rescue in mammalian mitochondria. Scientific Reports. # TORREGROSA-MUÑUMER R, FORSLUND J, GOFFART S, STOJKOVIC G, PFEIFFER A, CARVALHO G,BLANCO L, WANROOIJ S & POHJOISMÄKI J. (2017). PrimPol is required for replication re-initiation aftermitochondrial DNA damage. PNAS. # TORREGROSA-MUÑUMER R, GOFFART S, HAIKONEN J, AND POHJOISMÄKI J. (2015). Low doses of UV and oxidative damage induce dramatic accumulation of mitochondrial DNA replication intermediates, forkregression and replication initiation shift. Mol Biol Cell. ID: 393
mtDNA maintenance and expression Loss of RNase H1 in early B cell development induces mitochondrial-based dysfunction 1DIR Eunice Kennedy Shriver National Institute of Child Health and Human Devlopment; 2Department of Molecular and Cellular Biology, University of Califofnia, Davis Bibliography
Cerritelli SM, Sakhuja K, Crouch RJ. RNase H1, the Gold Standard for R-Loop Detection. Methods Mol Biol. 2022;2528:91-114. doi: 10.1007/978-1-0716-2477-7_7. PMID: 35704187. ID: 212
mtDNA maintenance and expression New insights into late-maturation steps of the human mitochondrial small ribosomal subunit 1Department of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany; 2Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Goettingen, Goettingen, Germany ID: 522
mtDNA maintenance and expression Early-stages during large mitoribosomal subunit assembly 1University Medical Center Göttingen, Germany; 2Cluster of Excellence (MBExC), University of Göttingen, Germany ID: 346
mtDNA maintenance and expression Effect of post-transcriptional modifications of tRNAMet on mitochondrial codon recognition Max Planck Institute of Multidisciplinary Sciences, Göttingen, Germany ID: 210
mtDNA maintenance and expression Establishing the OPA1 role in the mtDNA maintenance in cell models of Dominant Optic Atrophy (DOA) 1IRCCS, Istituto delle Scienze Neurologiche di Bologna, Italy - Programma di Neurogenetica; 2DIBINEM, Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy; 3Vall d'Hebron Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Raras-CIBERER, Autonomous University of Barcelona, Barcelona, Spain ID: 325
mtDNA maintenance and expression Mutations affecting the relation between mtDNA synthesis and proofreading by POLγ Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-405 30 Gothenburg, Sweden ID: 306
mtDNA maintenance and expression Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation 1Genetics Section, Molecular and Clinical Sciences, St George’s, University of London, London, United Kingdom; 2Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 3Research Programs Unit, Molecular Neurology, Biomedicum, University of Helsinki, • Helsinki, Finland; 4Department of Immunology, Institute of Clinical Medicine, University of Oslo and Oslo, University Hospital, Oslo, Norway; 5Core Facilities, St George’s, University of London, London, United Kingdom.; 6Wellcome Centre for Mitochondrial Research, Translational and Clinical Research • Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 7NHS Highly Specialised Service for Rare Mitochondrial Disorders, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 8Department of Genetics, Hadassah Medical Center & Faculty of Medicine, Hebrew University of Jerusalem. 9112001 Jerusalem Israel.; 9Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 10Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; 11Institute of Biotechnology, University of Helsinki, Helsinki, Finland ID: 302
mtDNA maintenance and expression The role of mL45 N-terminus in mitochondrial translation under standard and stress conditions Department of Neurology, University of Miami, Miller School of Medicine, FL, USA ID: 314
mtDNA maintenance and expression Characterization of human mitochondrial translation elongation and ribosome recycling factors mtEFG1 and mtEFG2 Max-Planck Institute for Multidisciplinary Sciences, Germany ID: 538
mtDNA maintenance and expression Knock-out of OGG1 in HEK293 cells does not alter the formation of single strand breaks in mitochondrial DNA upon H2O2 treatment 1Institute of Experimental Epileptology and Cognition Research, University of Bonn, Germany; 2Department of Epileptology, University Hospital Bonn, Germany ID: 455
mtDNA maintenance and expression Ligase 3 is indispensable for repair of oxidative lesions of mtDNA but dispensable for circular genome end ligation University Bonn, Department of Epileptology, Germany Bibliography
1. Zsurka G, Trombly G, Schöler S, Blei D, Kunz WS. Functional Assessment of Mitochondrial DNA Maintenance by Depletion and Repopulation Using 2',3'-Dideoxycytidine in Cultured Cells. Methods Mol Biol. 2023;2615:229-240 2. Mikhailova AG, Mikhailova AA, Ushakova K, Tretiakov EO, Iliushchenko D, Shamansky V, Lobanova V, Kozenkov I, Efimenko B, Yurchenko AA, Kozenkova E, Zdobnov EM, Makeev V, Yurov V, Tanaka M, Gostimskaya I, Fleischmann Z, Annis S, Franco M, Wasko K, Denisov S, Kunz WS, Knorre D, Mazunin I, Nikolaev S, Fellay J, Reymond A, Khrapko K, Gunbin K, Popadin K. A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand. Nucleic Acids Res. 2022 Oct 14;50(18):10264-10277 3. Hippen M, Zsurka G, Peeva V, Machts J, Schwiecker K, Debska-Vielhaber G, Wiesner RJ, Vielhaber S, Kunz WS. Novel Pathogenic Sequence Variation m.5789T>C Causes NARP Syndrome and Promotes Formation of Deletions of the Mitochondrial Genome. Neurol Genet. 2021 Mar 3;8(2):e660. 4. Birtel J, von Landenberg C, Gliem M, Gliem C, Reimann J, Kunz WS, Herrmann P, Betz C, Caswell R, Nesbitt V, Kornblum C, Charbel Issa P. Mitochondrial Retinopathy. Ophthalmol Retina. 2022 Jan;6(1):65-79. 5. Rotko D, Kudin AP, Zsurka G, Kulawiak B, Szewczyk A, Kunz WS. Molecular and Functional Effects of Loss of Cytochrome c Oxidase Subunit 8A. Biochemistry (Mosc). 2021 Jan;86(1):33-43. 6. Torregrosa-Muñumer R, Hangas A, Goffart S, Blei D, Zsurka G, Griffith J, Kunz WS, Pohjoismäki JLO. Replication fork rescue in mammalian mitochondria. Sci Rep. 2019 Jun 19;9(1):8785. 7. Peeva V, Blei D, Trombly G, Corsi S, Szukszto MJ, Rebelo-Guiomar P, Gammage PA, Kudin AP, Becker C, Altmüller J, Minczuk M, Zsurka G, Kunz WS. Linear mitochondrial DNA is rapidly degraded by components of the replication machinery. Nat Commun. 2018 Apr 30;9(1):1727. ID: 237
mtDNA maintenance and expression Modulation of mtDNA heteroplasmy through endosomal-mitophagy 1Institute of Physiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; 2Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; 3Institute of Genetics, University of Cologne, Germany Bibliography
1. Endosomal-dependent mitophagy coordinates mitochondrial nucleoid and mtDNA elimination. Autophagy. 2023 Jan 29;1-2. doi: 10.1080/15548627.2023.2170959 2. Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA. Nat Commun. 2022 Nov 7;13(1):6704. doi: 10.1038/s41467-022-34205-9. 3. Combined fibre atrophy and decreased muscle regeneration capacity driven by mitochondrial DNA alterations underlie the development of sarcopenia. Journal Cachexia Sarcopenia Muscle. 2022 Aug;13(4):2132-2145. doi: 10.1002/jcsm.13026. Epub 2022 Jun 28. ID: 503
mtDNA maintenance and expression The role of mitoSAM in mitochondrial gene expression 1Division of Molecular Metabolism, Karolinska Institutet, Stockholm, Sweden; 2Max Planck Institute of Biochemistry, Munich, Germany; 3Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Sweden; 4Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden; 5Proteomics Core Facility, Max Planck Institute for Biology of Ageing, Cologne, Germany ID: 634
mtDNA maintenance and expression The slumbering mitochondrion awakes: monitoring mitochondrial gene expression during oocyte and early embryo development 1Newcastle Fertility Centre, International Centre for Life, Newcastle upon Tyne, NE1 3BZ, United Kingdom; 2Wellcome Centre for Mitochondrial Research, Newcastle University Biosciences Institute, Newcastle upon Tyne, NE2 4HH, United Kingdom Bibliography
Zorkau M, Albus CA, Berlinguer-Palmini R, Chrzanowska-Lightowlers ZMA, Lightowlers RN. High-resolution imaging reveals compartmentalization of mitochondrial protein synthesis in cultured human cells. Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2008778118. Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011 Sep;11(5):797-813. De La Fuente R, Eppig JJ. Transcriptional activity of the mouse oocyte genome: companion granulosa cells modulate transcription and chromatin remodeling. Dev Biol. 2001;229(1):224-36. Heyn P, Kircher M, Dahl A, Kelso J, Tomancak P, Kalinka AT, Neugebauer KM. The earliest transcribed zygotic genes are short, newly evolved, and different across species. Cell Rep. 2014 Jan 30;6(2):285-92. Cheng S, Altmeppen G, So C, Welp LM, Penir S, Ruhwedel T, Menelaou K, Harasimov K, Stützer A, Blayney M, Elder K, Möbius W, Urlaub H, Schuh M. Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment. Science. 2022 Oct 21;378(6617):eabq4835. Garcia-Alonso, L., Lorenzi, V., Mazzeo, C.I. et al. Single-cell roadmap of human gonadal development. Nature 607, 540–547 (2022). ID: 373
mtDNA maintenance and expression How mitochondrial DNA metabolism shapes cellular senescence Department of Medical Biochemistry and Biophysics, Umeå University, Umeå 90736, Sweden Bibliography
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mtDNA maintenance and expression Processing of stalled replication forks in mitochondria University of Eastern Finland, Finland ID: 496
mtDNA maintenance and expression Stochastic survival of the densest accounts for the expansion of mitochondrial mutations in the ageing of skeletal muscle fibres 1Department of Mathematics, Imperial College London, United Kingdom; 2EPSRC Centre for the Mathematics of Precision Healthcare, Imperial College London, United Kingdom Bibliography
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mtDNA maintenance and expression Top3α is the replicative topoisomerase in mitochondrial DNA replication 1University of Eastern Finland, Finland; 2Radboud Center for Mitochondrial Medicine, Department of Paediatrics, Radboudumc, Nijmegen, The Netherlands ID: 260
mtDNA maintenance and expression Mitochondrial-nuclear compatibility in hare cybrids 1University of Eastern Finland, Finland; 2Tampere University, Finland ID: 339
mtDNA maintenance and expression Identification of drugs for the treatment of POLG-related diseases by means of a high throughput drug repurposing approach performed in Saccharomyces cerevisiae 1Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; 2Department of Biology, University of Padova, Padova, Italy Bibliography
Magistrati M., Gilea A.I., Ceccatelli Berti C., Baruffini E., Dallabona C. (2023) Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models. Int J Mol Sci. 24:2178. doi: 10.3390/ijms24032178. (Corresponding author) Gilea A.I., Ceccatelli Berti C., Magistrati M., di Punzio G., Goffrini P., Baruffini E., Dallabona C. (2021) Saccharomyces cerevisiae as a Tool for Studying Mutations in Nuclear Genes Involved in Diseases Caused by Mitochondrial DNA Instability. Genes (Basel). 12:1866. doi: 10.3390/genes12121866. (Corresponding author) di Punzio G., Gilberti M., Baruffini E., Lodi T., Donnini C., Dallabona C. (2021) A Yeast-Based Repurposing Approach for the Treatment of Mitochondrial DNA Depletion Syndromes Led to the Identification of Molecules Able to Modulate the dNTP Pool. Int. J. Mol. Sci. 22:12223. doi: 10.3390/ijms222212223. Cappuccio G., Ceccatelli Berti C., Baruffini E., Sullivan J, Shashi V., Jewett T, Stamper T., Maitz S., Canonico F., Revah-Politi A., Kupchik G.S., Anyane-Yeboa K., Aggarwal V., Benneche A., Bratland E., Berland S., D'Arco F., Alves C.A., Vanderver A., Longo D., Bertini E., Torella A., Nigro V.; D'Amico A., van der Knaap M.S., Goffrini P., Brunetti-Pierri N. (2021) Bi-allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease. Hum. Mutat. 42:745-761. doi: 10.1002/humu.24210. (Co-first author) Figuccia S., Degiorgi A., Ceccatelli Berti C., Baruffini E., Dallabona C., Goffrini P. (2021) Mitochondrial Aminoacyl-tRNA Synthetase and Disease: The Yeast Contribution for Functional Analysis of Novel Variants. Int. J. Mol. Sci. 22:4524. doi: 10.3390/ijms22094524. Hytönen M.K., Sarviaho R., Jackson C.B., Syrjä P., Jokinen T., Matiasek K., Rosati M., Dallabona C., Baruffini E., Quintero I., Arumilli M., Monteuuis G., Donner J., Anttila M., Suomalainen A., Bindoff LA., Lohi H. (2021) In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration. Hum. Genet. 140:1593-1609. doi: 10.1007/s00439-021-02279-y. Ceccatelli Berti C., di Punzio G., Dallabona C., Baruffini E., Goffrini P., Lodi T., Donnini C. (2021) The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases. Genes (Basel). 12:300. doi: 10.3390/genes12020300. Facchinello N., Laquatra C., Locatello L., Beffagna G., Brañas Casas R., Fornetto C., Dinarello A., Martorano L., Vettori A., Risato G., Celeghin R., Meneghetti G., Santoro M.M., Delahodde A., Vanzi F., Rasola A., Dalla Valle L., Rasotto M.B., Lodi T., Baruffini E., Argenton F., Tiso N. (2021) Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish. Cell. Death Dis. 12:100. doi: 10.1038/s41419-020-03359-z. (Co-corresponding author) Aleo S.J., Del Dotto V., Fogazza M., Maresca A., Lodi T., Goffrini P., Ghelli A., Rugolo M., Carelli V., Baruffini E., Zanna C. (2021) Drug repositioning as a therapeutic strategy for neurodegenerations associated with OPA1 mutations. Hum. Mol. Genet. 29:3631-3645. doi: 10.1093/hmg/ddaa244. (Co-senior author) Benincá C., Zanette V., Brischigliaro M., Johnson M., Reyes A., Valle D.A.D., J Robinson A., Degiorgi A., Yeates A., Telles B.A., Prudent J., Baruffini E., S. F. Santos M.L., R. de Souza R.L., Fernandez-Vizarra .E, Whitworth A.J., Zeviani M. (2021) Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features. J. Med. Genet. 58:155-167. doi: 10.1136/jmedgenet-2020-106861. Hoyos-Gonzalez N., Trasviña-Arenas C.H., Degiorgi A., Castro-Lara A.Y., Peralta-Castro A., Jimenez-Sandoval P., Diaz-Quezada C., Lodi T., Baruffini E., Brieba LG. (2020) Modeling of pathogenic variants of mitochondrial DNA polymerase: insight into the replication defects and implication for human disease. Biochim. Biophys. Acta Gen. Subj. 1864:129608. doi: 10.1016/j.bbagen.2020.129608. (Co-corresponding author) Trasviña-Arenas C.H., Hoyos-Gonzalez N., Castro-Lara A.I., Rodriguez-Hernandez A., Sanchez-Sandoval M.E., Jimenez-Sandoval P., Ayala-García V.M., Díaz-Quezada C., Lodi T., Baruffini E., Brieba L.G. (2019) Amino and carboxy-terminal extensions of yeast mitochondrial DNA polymerase assemble both the polymerization and exonuclease active sites. Mitochondrion, 49:166-177. doi: 10.1016/j.mito.2019.08.005. ISSN: 1567-7249 Chin H., Goh D.L., Wang F.S, Hong Tay S.K., Heng C.K., Donnini C., Baruffini E., Pines O. 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Therapy 1: preclinical developments Mitochondrial genome replacement can rejuvenate aging cells Kyoto prefectural University of Medicine, Japan Bibliography
1: Suzuki Y, Kami D, Taya T, Sano A, Ogata T, Matoba S, Gojo S. ZLN005 improves the survival of polymicrobial sepsis by increasing the bacterial killing via inducing lysosomal acidification and biogenesis in phagocytes. Front Immunol. 2023 Feb 3;14:1089905. doi: 10.3389/fimmu.2023.1089905. 2: Kami D, Ishizaki T, Taya T, Katoh A, Kouji H, Gojo S. A novel mRNA decay inhibitor abolishes pathophysiological cellular transition. Cell Death Discov. 2022 Jun 7;8(1):278. doi: 10.1038/s41420-022-01076-4. 3: Shikuma A, Kami D, Maeda R, Suzuki Y, Sano A, Taya T, Ogata T, Konkel A, Matoba S, Schunck WH, Gojo S. Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids. Front Immunol. 2022 Feb 24;13:825171. doi: 10.3389/fimmu.2022.825171. 4: Maeda R, Kami D, Shikuma A, Suzuki Y, Taya T, Matoba S, Gojo S. RNA decay in processing bodies is indispensable for adipogenesis. Cell Death Dis. 2021 Mar 17;12(4):285. doi: 10.1038/s41419-021-03537-7. ID: 399
Therapy 1: preclinical developments Project pearl: raising the profile of mitochondrial disease Wellcome Centre for Mitochondrial Research, Newcastle University, United Kingdom Bibliography
Rhys H. Thomas, Amy Hunter, Lyndsey Butterworth, Catherine Feeney, Tracey D. Graves, Sarah Holmes, Pushpa Hossain, Jo Lowndes, Jenny Sharpe, Sheela Upadhyaya, Kristin N. Varhaug, Marcela Votruba, Russell Wheeler, Kristina Staley, Shamima Rahman. Research priorities for mitochondrial disorders: Current landscape and patient and professional views. J Inherit Metab Dis. 2022 Jul;45(4):796-803. doi: 10.1002/jimd.12521. Craven L, Murphy JL, Turnbull DM. Mitochondrial donation - hope for families with mitochondrial DNA disease. Emerg Top Life Sci. 2020 Sep 8;4(2):151-154. doi: 10.1042/ETLS20190196. Ahmed ST, Craven L, Russell OM, Turnbull DM, Vincent AE. Diagnosis and Treatment of Mitochondrial Myopathies. Neurotherapeutics. 2018 Oct;15(4):943-953. doi: 10.1007/s13311-018-00674-4. Rai PK, Craven L, Hoogewijs K, Russell OM, Lightowlers RN. Advances in methods for reducing mitochondrial DNA disease by replacing or manipulating the mitochondrial genome. Essays Biochem. 2018 Jul 20;62(3):455-465. doi: 10.1042/EBC20170113. Craven L, Murphy J, Turnbull DM, Taylor RW, Gorman GS McFarland R. Scientific and Ethical Issues in Mitochondrial Donation. The New Bioethics. In publication. Craven L*, Tang MX*, Gorman GS, De Sutter P, Heindryckx B. Novel reproductive technologies to prevent mitochondrial disease. Hum Reprod Update. 2017 23:1-19. doi: 10.1093/humupd/dmx018. Craven L, Alston CL, Taylor RW, Turnbull DM. Recent Advances in Mitochondrial Disease. Annu Rev Genomics Hum Genet. 2017 Aug 31;18:257-275. doi: 10.1146/annurev-genom-091416-035426. Hyslop LA, Blakeley P, Craven L, et al. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature. 2016 16;534 (7607):383-6. doi: 10.1038/nature18303. Craven L, Herbert M, Murdoch A, Murphy J, Lawford Davies J, Turnbull DM. Research into Policy: A Brief History of Mitochondrial Donation. Stem Cells. 2016 Feb;34(2):265-7. doi: 10.1002/stem.2221. Chinnery PF, Craven L, Mitalipov S, Stewart JB, Herbert M, Turnbull DM. The challenges of mitochondrial replacement. PLoS Genet. 2014 Apr 24;10(4):e1004315. doi: 10.1371/journal.pgen.1004315. Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010 6;465 (7294):82-5. doi: 10.1038/nature08958. ID: 113
Therapy 1: preclinical developments Innovative technology for regulating mitochondrial function in host cells 1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; 2FOREST Program, Japan Science and Technology Agency Japan, Saitama, Japan; 3Faculty of Engineering, Hokkaido University, Sapporo, Japan; 4Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Bibliography
Yamada Y, Munechika R, Satrialdi, Kubota F, Sato Y, Sakurai Y, Harashima H, Mitochondrial delivery of an anticancer drug via systemic administration using a mitochondrial delivery system that inhibits the growth of drug-resistant cancer engrafted on mice. J. Pharm. Sci. ;109: 2493-2500 (2020). Yamada Y, Somiya K, Miyauchi A, Osaka H, Harashima H, Validation of a mitochondrial RNA therapeutic strategy using fibroblasts from a Leigh syndrome patient with a mutation in the mitochondrial ND3 gene. Sci. Rep. 10: 7511 (2020). Yamada Y, Maruyama M, Kita T, Usami S, Kitajiri S, Harashima H, The use of a MITO-Porter to deliver exogenous therapeutic RNA to a mitochondrial disease’s cell with a A1555G mutation in the mitochondrial 12S rRNA gene results in an increase in mitochondrial respiratory activity. Mitochondrion 55: 134-144 (2020). Yamada Y, Satrialdi, Hibino M, Sasaki D, Jiro A, Harashima H. Power of mitochondrial drug delivery systems to produce innovative nanomedicines. Adv. Drug. Deliv. Rev. 154-155： 187-209 (2020). Sasaki D, Abe J, Takeda A, Harashima H, Yamada Y, Transplantation of MITO cells, mitochondria activated cardiac progenitor cells, to the ischemic myocardium of mouse enhances the therapeutic effect. Sci. Rep. 12: 4344 (2022). Yamada Y, Sato Y, Nakamura T, Harashima H. Innovative cancer nanomedicine based on immunology, gene editing, intracellular trafficking control J. Control. Release 348: 357-369 (2022). ID: 153
Therapy 1: preclinical developments CNS gene therapy in a mouse model of complex I encephalopathy University of Miami, United States of America Bibliography
Walker, BR, Moraes, CT. Nuclear-Mitochondrial Interactions. Biomolecules, 2022, 12, 427. https://doi.org/10.3390/biom12030427 ID: 515
Therapy 1: preclinical developments Strategies for fighting mitochondrial diseases: AAV-based gene therapy 1Venetian Institute of Molecular Medicine, Padova; 2Department of Neuroscience, University of Padova; 3Department of Biomedical Sciences, University of Padova ID: 660
Therapy 1: preclinical developments Cannabidiol ameliorates mitochondrial disease via PPARgamma activation 1Neuroscience Institute, Autonomous University of Barcelona, Bellaterra, Spain; 2Minoryx Therapeutics SL, Barcelona, Spain; 3Celltec-UB, Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat de Barcelona, Barcelona, Spain; 4CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain ID: 151
Therapy 1: preclinical developments Sonlicromanol improves phenotypic changes in models of Selenoprotein N-related myopathies 1Khondrion, Nijmegen, The Netherlands; 2Department of Pediatrics, RCMM, RadboudUMC, Nijmegen, The Netherlands; 3Radboud University, Radboud Institute for Biological and Environmental Sciences, Cluster Ecology & Physiology, Department of Animal Physiology, Nijmegen, The Netherlands; 4Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; 5Department of Pediatric Neurology, Centre of neuromuscular disorders in children and adolescents, University Clinic Essen, University of Duisburg-Essen, Germany ID: 211
Therapy 1: preclinical developments Therapeutic interventions to regulate the Q-junction, 1C metabolism and the neuroinflammatory response. 1Physiology Department, Biomedical Research Center, University of Granada, Spain; 2Ibs. Granada, Granada, Spain Bibliography
1.Nikkanen, J., et al., Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism. Cell Metab, 2016. 23(4): p. 635-48. 2.Bao, X.R., et al., Mitochondrial dysfunction remodels one-carbon metabolism in human cells. eLife, 2016. 5: p. e10575. 3.Forsström, S., et al., Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA Deletions. Cell Metabolism, 2019. 30(6): p. 1040-1054.e7. 4.Krug, A.K., et al., Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+). Cell Death Dis, 2014. 5(5): p. e1222. 5.González-García, P., et al., Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism. Human molecular genetics, 2020. 29(19): p. 3296-3311. 6.Hidalgo-Gutierrez, A., et al., beta-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9 (R239X) mice. EMBO Mol Med, 2019. 11(1). 7.Gonzalez-Garcia, P., et al., The Q-junction and the inflammatory response are critical pathological and therapeutic factors in CoQ deficiency. Redox Biol, 2022. 55: p. 102403. ID: 350
Therapy 1: preclinical developments Yeast as a model for searching drugs against pathologies caused by mutations in ACO2 1Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy; 3Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna Bibliography
Magistrati M., Gilea A.I., Ceccatelli Berti C., Baruffini E., Dallabona C. (2023) Modopathies Caused by Mutations in Genes Encoding for Mitochondrial RNA Modifying Enzymes: Molecular Mechanisms and Yeast Disease Models. Int J Mol Sci. 24:2178. doi: 10.3390/ijms24032178. (Co-first author) Gilea A.I., Ceccatelli Berti C., Magistrati M., di Punzio G., Goffrini P., Baruffini E., Dallabona C. (2021) Saccharomyces cerevisiae as a Tool for Studying Mutations in Nuclear Genes Involved in Diseases Caused by Mitochondrial DNA Instability.Genes (Basel). 12:1866. doi: 10.3390/genes12121866. Ceccatelli Berti C., Gilea A.I., De Gregorio M.A., Goffrini P. (2020) Exploring Yeast as a Study Model of Pantothenate Kinase-Associated Neurodegeneration and for the Identification of Therapeutic Compounds.Int J Mol Sci. 22:293. doi: 10.3390/ijms22010293. ID: 577
Therapy 1: preclinical developments MiR-181a/b modulation as a potential therapeutic approach for Stargardt disease treatment 1Telethon Institute of Genetics and Medicine,Italy; 2Institute for Genetic and Biomedical Research, CNR, Italy; 3Department of Translational Medical Science Federico II University of Naples, Italy; 4University of Campania Luigi Vanvitelli, Italy; 5Ecosustainable Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Italy Bibliography
1) Jabri Y, Biber J, Diaz-Lezama N, Grosche A, Pauly D. Cell-Type-Specific Complement Profiling in the ABCA4-/- Mouse Model of Stargardt Disease. Int J Mol Sci. 2020 Nov 11;21(22):8468. doi: 10.3390/ijms21228468. PMID: 33187113; PMCID: PMC7697683. 2) Indrieri A, Carrella S, Romano A, Spaziano A, Marrocco E, Fernandez-Vizarra E, Barbato S, Pizzo M, Ezhova Y, Golia FM, Ciampi L, Tammaro R, Henao-Mejia J, Williams A, Flavell RA, De Leonibus E, Zeviani M, Surace EM, Banfi S, Franco B. miR-181a/b downregulation exerts a protective action on mitochondrial disease models. EMBO Mol Med. 2019 May;11(5):e8734. doi: 10.15252/emmm.201708734. PMID: 30979712; PMCID: PMC6505685. 3)Barbato A, Iuliano A, Volpe M, D'Alterio R, Brillante S, Massa F, De Cegli R, Carrella S, Salati M, Russo A, Russo G, Riccardo S, Cacchiarelli D, Capone M, Madonna G, Ascierto PA, Franco B, Indrieri A, Carotenuto P. Integrated Genomics Identifies miR-181/TFAM Pathway as a Critical Driver of Drug Resistance in Melanoma. Int J Mol Sci. 2021 Feb 11;22(4):1801. doi: 10.3390/ijms22041801. PMID: 33670365; PMCID: PMC7918089. 4) Carrella S, Indrieri A, Franco B, Banfi S. Mutation-Independent Therapies for Retinal Diseases: Focus on Gene-Based Approaches. Front Neurosci. 2020 Sep 24;14:588234. doi: 10.3389/fnins.2020.588234. PMID: 33071752; PMCID: PMC7541846. ID: 216
Therapy 1: preclinical developments MitoTALEN reduces mutant mtDNA load in the mouse CNS 1Department of Neurology, University of Miami Miller School of Medicine, Miami USA; 2Wellcome Centre for Mitochondrial Research, Biosciences Institute, Newcastle University, Newcastle UK Bibliography
MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation. Bacman SR, Kauppila JHK, Pereira CV, Nissanka N, Miranda M, Pinto M, Williams SL, Larsson NG, Stewart JB, Moraes CT. Nat Med. 2018 Nov;24(11):1696-1700. Mitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo. Zekonyte U, Bacman SR, Smith J, Shoop W, Pereira CV, Tomberlin G, Stewart J, Jantz D, Moraes CT. Nat Commun. 2021 May 28;12(1):3210. Precise and simultaneous quantification of mitochondrial DNA heteroplasmy and copy number by digital PCR. Shoop WK, Gorsuch CL, Bacman SR, Moraes CT. J Biol Chem. 2022 Nov;298(11):102574. ID: 519
Therapy 1: preclinical developments Phosphodiesterase 5 inhibitors (PDE5i) as a promising treatment for MT-ATP6 associated mater-nally inherited Leigh Syndrome (MILS) 1Charité-Universitätsmedizin Berlin, Department of Neuropediatrics, Berlin, Germany; 2Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine Universi-ty, Düsseldorf, Germany; 3Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, ScreeningPort, Hamburg, Germany; 4University of Verona, Italy; 5Fondazione IRCCS Instituto Neurologico "C. Besta", Milano, Italy; 6Ludwig Maximilians University (LMU), München, Germany; 7University of Bologna, Italy; 8Freie Universität Berlin, Germany Bibliography
[1]D. Leigh, “Subacute necrotizing encephalomyelopathy in a neonatal infant,” J. Neurol. Neurosurg. Psychiat., vol. 14, pp. 216–221, 1951, doi: 10.1097/00005072-197703000-00010. [2]S. Rahman, “Leigh syndrome,” in Handbook ofClinical Neurology, Mitochondrial Diseases, 3rd ed., vol. 194, R. Horvath, M. Hirano, and P. F. Chinnery, Eds. Elsevier B.V., 2023, pp. 43–63. [3]C. Lorenz et al., “Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6,” Stem Cell Res., vol. 61, p. 102742, 2022, doi: 10.1016/j.scr.2022.102742. [4]M.-T. Henke, A. Zink, S. Diecke, A. Prigione, and M. Schuelke, “Generation of two mother – child pairs of iPSCs from maternally inherited Leigh syndrome patients with m . 8993 T > G and m . 9176 T > G MT-ATP6 mutations,” Stem Cell Res., vol. 67, no. December 2022, pp. 1–5, 2023, doi: 10.1016/j.scr.2023.103030. [5]C. Lorenz et al., “Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders,” Cell Stem Cell, vol. 20, no. 5, pp. 659-674.e9, 2017, doi: 10.1016/j.stem.2016.12.013. ID: 562
Therapy 1: preclinical developments The effect of mitochondrial NMNAT3 overexpression on Alzheimer’s related proteinopathies University of Miami, United States of America Bibliography
1.Zhu, Y., et al., Human Nmnat1 Promotes Autophagic Clearance of Amyloid Plaques in a Drosophila Model of Alzheimer's Disease. Front Aging Neurosci, 2022. 14: p. 852972. 2.Huang, C., et al., The mouse nicotinamide mononucleotide adenylyltransferase chaperones diverse pathological amyloid client proteins. J Biol Chem, 2022. 298(5): p. 101912. ID: 547
Therapy 1: preclinical developments In vitro models to test modulators of cellular NAD+ levels 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2UCL School of Pharmacy, UCL, London, UK; 3NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK ID: 417
Therapy 1: preclinical developments Novel small molecule improves mitochondrial function and mitophagy in a complex III deficiency model. 1Department of Medicine, Division of Endocrinology, David Geffen School of Medicine, Los Angeles, USA.; 2Capacity Bio, Los Angeles, USA; 3Department of Pharmacology, Center for Innovations in Brain Science, University of Arizona, USA; 4Institut de Biologia Molecular De Barcelona (IBMB-CSIC), Spain.; 5Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, USA Bibliography
Fernandez-del-Rio L, Benincá C, Villalobos F, Shu C, Liesa-Roig M, Stiles L, Acín-Perez R, Shirihai OS. A Novel Approach to Measure Complex V ATP Hydrolysis in Frozen Cell Lysates and Tissue Homogenates (in press; Life Science Alliance Journal) Acín-Perez R, Benincá C, Shabane B, Shirihai OS, Stiles L. Utilization of Human Samples for Assessment of Mitochondrial Bioenergetics: Gold Standards, Limitations, and Future Perspectives. Life (Basel). 2021 Sep 10;11(9):949. doi: 10.3390/life11090949. PMID: 34575097; PMCID: PMC8467772. Zanette V, Valle DD, Telles BA, Robinson AJ, Monteiro V, Santos MLSF, Souza RLR, Benincá C. NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms. Genet Mol Biol. 2021 Nov 19;44(4):e20210149. doi: 10.1590/1678-4685-GMB-2021-0149. PMID: 34807224; PMCID: PMC8607527. Gaddale Devanna KK , Gawel JM , Prime TA , Cvetko F , Benincá C , Caldwell ST , Negoda A , Harrison A , James AM , Pavlov EV , Murphy MP , Hartley RC . Tetra-arylborate lipophilic anions as targeting groups. Chem Commun (Camb). 2021 Mar 28;57(25):3147-3150. doi: 10.1039/d0cc07924c. Epub 2021 Feb 26. PMID: 33634803; PMCID: PMC8062962. Peruzzotti-Jametti L, Bernstock JD, Willis CM, Manferrari G, Rogall R, Fernandez-Vizarra E, Williamson JC, Braga A, van den Bosch A, Leonardi T, Krzak G, Kittel Á, Benincá C, Vicario N, Tan S, Bastos C, Bicci I, Iraci N, Smith JA, Peacock B, Muller KH, Lehner PJ, Buzas EI, Faria N, Zeviani M, Frezza C, Brisson A, Matheson NJ, Viscomi C, Pluchino S. Neural stem cells traffic functional mitochondria via extracellular vesicles. PLoS Biol. 2021 Apr;19(4):e3001166. doi: 10.1371/journal.pbio.3001166. eCollection 2021 Apr. PubMed PMID: 33826607; PubMed Central PMCID: PMC8055036. Benincá C, Zanette V, Brischigliaro M, Johnson M, Reyes A, Valle DAD, J Robinson A, Degiorgi A, Yeates A, Telles BA, Prudent J, Baruffini E, S F Santos ML, R de Souza RL, Fernandez-Vizarra E, J Whitworth A, Zeviani M. Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features. J Med Genet. 2021 Mar;58(3):155-167. doi: 10.1136/jmedgenet-2020-106861. Epub 2020 May 21. PMID: 32439808; PMCID: PMC7116790. Zanette V, Reyes A, Johnson M, do Valle D, Robinson AJ, Monteiro V, Telles BA, L R Souza R, S F Santos ML, Benincá C, Zeviani M. Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations. Neurol Genet. 2020 Oct 7;6(6):e521. doi: 10.1212/NXG.0000000000000521. PMID: 33134517; PMCID: PMC7577545. Luna-Sanchez M, Benincá C, Cerutti R, Brea-Calvo G, Yeates A, Scorrano L, Zeviani M, Viscomi C. Opa1 Overexpression Protects from Early-Onset Mpv17-/--Related Mouse Kidney Disease. Mol Ther. 2020 Aug 5;28(8):1918-1930. doi: 10.1016/j.ymthe.2020.06.010. Epub 2020 Jun 12. PMID: 32562616; PMCID: PMC7403474. ID: 270
Therapy 1: preclinical developments Preservation of bioenergetics and inhibition of ferroptosis with the novel compound SBT-588 in Friedreich’s Ataxia cell models Stealth BioTherapeutics, Needham, MA, United States of America Bibliography
1.McNeil, B., Beck, L., Sullivan, A., Kropp, LE., Abbruscato, A., Bergheanu, SC. Interventions with Potential to Mitigate Injection Site Reactions Following Subcutaneous Elamipretide Administration: Phase 1, Crossover Study in Healthy Subjects (In preparation). 2.Kropp, LE., Thomas, LM, Jackson-Thompson, B., Gable, K., McDaniels, D., Mitre, E., Chronic infection with a tissue invasive helminth causes mast cell granule depletion and protects against systemic anaphylaxis Clinical & Experimental Allergy. 2019 Dec 13. doi: 10.1111/cea.13549. Epub 2020 Jan 15. 3.Abdeladhim, M., Zhang, AH., Kropp, LE., Lindrose, AR., Venkatesha, SH., Mitre, E., Scott, DW. Engineered ovalbumin-expressing regulatory T cells protect against anaphylaxis in ovalbumin-sensitized mice. Clinical Immunology. 2019 Oct;207:49-54. doi: 10.1016/j.clim.2019.07.009. Epub 2019 Jul 17. 4.Killoran, K.*, Kropp, LE.*, Lindrose, A., Curtis, H., Cook, D., Mitre, E., Rush desensitization with a single antigen induces subclinical activation of mast cells and protects against bystander challenge in dually sensitized mice. Clinical & Experimental Allergy. 2019 Apr;49(4):484-494. doi: 10.1111/cea.13323. Epub 2019 Jan 16. a.*contributed equally to the manuscript ID: 109
Therapy 1: preclinical developments The use of a coenzyme Q10 encapsulated mitochondrial targeting lipid nanoparticle formulation has therapeutic effects on a drug-induced liver injury. 1Faculty of Pharmaceutical Sciences, Hokkaido University, Japan; 2Faculty of Engineering, Hokkaido University, Japan; 3Fusion Oriented REsearch for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan Bibliography
1)Yuma Yamada, Satrialdi, Mitsue Hibino, Daisuke Sasaki, Jiro Abe, Hideyoshi Harashima, Power of mitochondrial drug delivery systems to produce innovative nanomedicines, Adv Drug Deliv Rev,154-155:187-209 (2020). 2)Yuma Yamada, Momo Ito, Manae Arai, Mitsue Hibino, Takao Tsujioka, Hideyoshi Harashima, Challenges in Promoting Mitochondrial Transplantation Therapy, Int J Mol Sci, 21(17):6365 (2020). 3)Yuma Yamada, Yuta Takano, Satrialdi, Jiro Abe, Mitsue Hibino, Hideyoshi Harashima, Therapeutic Strategies for Regulating Mitochondrial Oxidative Stress, Biomolecules, 10(1):83 (2020). 4)Eriko Kawamura, Mitsue Hibino, Hideyoshi Harashima, Yuma Yamada, Targeted mitochondrial delivery of antisense RNA-containing nanoparticles by a MITO-Porter for safe and efficient mitochondrial gene silencing, Mitochondrion, 49, 178-188 (2019). 5)Takashi Katayama, Shintaro Kinugawa, Shingo Takada, Takaaki Furihata, Arata Fukushima, Takashi Yokota, Toshihisa Anzai, Mitsue Hibino, Hideyoshi Harashima, Yuma Yamada, A mitochondrial delivery system using liposome-based nanocarriers that target myoblast cells, Mitochondrion, 49, 66-72 (2019). 6)Mitsue Hibino, Yuma Yamada, Naoki Fujishita, Yusuke Sato, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima, The use of a microfluidic device to encapsulate a poorly water-soluble drug CoQ10 in lipid nanoparticles and an attempt to regulate intracellular trafficking to reach mitochondria, J Pharm Sci, 108 (8), 1668-2676 (2019). ID: 321
Therapy 1: preclinical developments In vitro 3D model of mitochondrial myopathy human skeletal muscle 1Wellcome Centre for Mitochondrial Research, Medical School, Newcastle University, United Kingdom; 2Translational and Clinical Research Institute, Newcastle University, United Kingdom; 3Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain; 4NHS Highly Specialised Service for Rare Mitochondrial Disorders, Royal Victoria Infirmary Bibliography
1Di Leo V, Lawless C, Newman J, Robertson F, Chun C, Pickett S, Hudson G, Gorman GS, Tuppen HA, Vincent AE & Russell OM. Resistance exercise training induces molecular changes in mitochondrial myopathy patients. Manuscript in preparation. 2Fernández-Costa JM, Fernández-Garibay X, Velasco-Mallorquí F, Ramón-Azcón J. Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies. J Tissue Eng. 2021 Feb 10;12:2041731420981339. 3Rocha MC, Grady JP, Grünewald A, Vincent A, Dobson PF, Taylor RW, Turnbull DM, Rygiel KA. A novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis. Sci Rep. 2015 Oct 15;5:15037. 413Fernández-Costa JM, Fernández-Garibay X, Velasco-Mallorquí F, Ramón-Azcón J. Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies. J Tissue Eng. 2021 Feb 10;12:2041731420981339. 5Trevelyan AJ, Kirby DM, Smulders-Srinivasan TK, Nooteboom M, Acin-Perez R, Enriquez JA, Whittington MA, Lightowlers RN, Turnbull DM. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain. 2010 Mar;133(Pt 3):787-96. 6He L, Chinnery PF, Durham SE, Blakely EL, Wardell TM, Borthwick GM, Taylor RW, Turnbull DM. Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR. Nucleic Acids Res. 2002 Jul 15;30(14):e68. 7Lehmann D, Tuppen HAL, Campbell GE, Alston CL, Lawless C, Rosa HS, Rocha MC, Reeve AK, Nicholls TJ, Deschauer M, Zierz S, Taylor RW, Turnbull DM, Vincent AE. Understanding mitochondrial DNA maintenance disorders at the single muscle fibre level. Nucleic Acids Res. 2019 Aug 22;47(14):7430-7443. 8Fernández-Garibay X, Ortega MA, Cerro-Herreros E, Comelles J, Martínez E, Artero R, Fernández-Costa JM, Ramón-Azcón J. Bioengineeredin vitro3D model of myotonic dystrophy type 1 human skeletal muscle. Biofabrication. 2021 Apr 26;13(3). ID: 449
Therapy 1: preclinical developments Metabolic consequences for NAD+ and N- Acetyl cysteine treatment on Mitochondrial myopathy 1STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; 2Diabetes and Obesity Research Unit, Research Programs Unit, University of Helsinki, FIN-00290 Helsinki, Finland; 3Laboratory of Integrative Systems Physiology, École polytechnique fédérale de Lausanne, Lausanne, Switzerland; 4Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; 5Helsinki University Hospital Diagnostic Centre, Helsinki 00260, Finland ID: 205
Therapy 1: preclinical developments Silencing the aberrant Coq9 mRNA in the Coq9R239X model normalizes complex Q and restores the mitochondrial phenotype. 1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs.Granada, Spain; 3Biofisika Institute (CSIC,UPV-EHU) and Department of Biochemistry and Molecular Biology, University of Basque Country, Leioa, Spain Bibliography
1.Luna‐Sánchez M, Díaz‐Casado E, Barca E, et al. The clinical heterogeneity of coenzyme Q 10 deficiency results from genotypic differences in the Coq9 gene. EMBO Mol Med. 2015;7(5):670-687. doi:10.15252/emmm.201404632 2.Wu H, Lima WF, Zhang H, Fan A, Sun H, Crooke ST. Determination of the Role of the Human RNase H1 in the Pharmacology of DNA-like Antisense Drugs. J Biol Chem. 2004;279(17):17181-17189. doi:10.1074/jbc.M311683200 ID: 380
Therapy 1: preclinical developments A high-content in vitro screening to identify new mitophagy-activating compounds 1Department of Biomedical Sciences, University of Padova, Italy; 2Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, USA; 3Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, USA ID: 285
Therapy 1: preclinical developments B-RA targets mitochondria in white adipose tissue and reverses diet-induced obesity 1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs. Granada, Granada, Spain Bibliography
1. Fazakerley DJ, et al. Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. Elife. 2018 Feb 6;7:e32111. doi: 10.7554/eLife.32111. 2.Hidalgo-Gutiérrez A, et al. β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight. Biomedicines. 2021 Oct 13;9(10):1457. doi: 10.3390/biomedicines9101457. ID: 378
Therapy 1: preclinical developments HIF1α is a potentially druggable target for MNGIE disease Alma Mater Studiorum University of Bologna, Italy ID: 627
Therapy 1: preclinical developments Mitochondrial modulation with Leriglitazone as a potential treatment for Rett syndrome Institut de Recerca Sant Joan de Déu, Spain ID: 204
Therapy 1: preclinical developments New nutritional therapies for mitochondrial diseases 1Mitochondrial and Neuromuscular Diseases Laboratory, Instituto de Investigación Sanitaria Hospital ‘12 de Octubre’ (‘imas12’), Madrid, Spain; 2Spanish Network for Biomedical Research in Rare Diseases (CIBERER), U723, Spain; 3Servicio de Genética, Hospital Universitario ‘12 de Octubre’, Madrid, Spain.; 4Unidad Pediátrica de Enfermedades Raras, Hospital Universitario ‘12 de Octubre’, Madrid, Spain.; 5Servicio de Medicina Interna, Hospital Universitario ‘12 de Octubre’, Madrid, Spain; 6Servicio de Neurología, Hospital Universitario ‘12 de Octubre’, Madrid, Spain; 7Centro Nacional de Referencia para Errores Congénitos del Metabolismo (CSUR) y Centro Europeo de Referencia para Enfermedades Metabólica Hereditarias (MetabERN), Madrid, Spain ID: 245
Therapy 1: preclinical developments Pyrroloquinoline quinone exerts neuroprotective effects on retinal ganglion cell degeneration 1Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden; 2Department of Biology, University of Pisa, Pisa, Italy Bibliography
1.Canovai A. Experimental model of photo-oxidative damage. Ann Eye Sci 2022. (doi: 10.21037/aes-21-50) 2.Canovai A. Experimental models of retinopathy of prematurity. Ann Eye Sci 2022. (doi: 10.21037/aes-21-49) 3.Canovai A., Amato R., Melecchi A., Dal Monte M., Rusciano D., Bagnoli P., Cammalleri M. Preventive Efficacy of an Antioxidant Compound on Blood Retinal Barrier Breakdown and Visual Dysfunction in Streptozotocin-Induced Diabetic Rats. Front. Pharmacol 2022;12:811818. (doi: 10.3389/fphar.2021.811818) 4.Pesce N.A.*, Canovai A.*, Plastino F., Lardner E., Kvanta A., Cammalleri M., André H., Dal Monte M. An imbalance in autophagy contributes to retinal damage in a rat model of oxygen-induced retinopathy. J Cell Mol Med 2021;25(22):10480-10493. (doi:10.1111/jcmm.16977) 5.Amato R.*, Canovai A.*, Melecchi A., Pezzino S., Corsaro R., Dal Monte M., Rusciano D., Bagnoli P., Cammalleri M. Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model. Biomedicines 2021; 9(9):1177. (doi: 10.3390/biomedicines9091177) 6.Pesce N.A., Canovai A., Lardner E., Cammalleri M., Kvanta A., André H., Dal Monte M. Autophagy Involvement in the Postnatal Development of the Rat Retina. Cells 2021;10(1):177. (doi: 10.3390/cells10010177) *Equal author contribution ID: 459
Therapy 1: preclinical developments Quinone compounds in primary mitochondrial disease: acute metabolic effects in human-derived cells in vitro 1Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; 2Department of Anesthesiology, Tokyo Medical University, Tokyo 160-0023, Japan; 3Abliva AB, Lund, Sweden ID: 259
Therapy 1: preclinical developments A novel therapeutic strategy for mitochondrial Leigh Syndrome 1Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.; 2Luca Science Inc., Tokyo, Japan.; 3Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.; 4Department of Hematology, Osaka International Cancer Institute, Osaka, Japan. Bibliography
1) Special AT-Rich Sequence-Binding Protein 1 Supports Survival and Maturation of Naive B Cells Stimulated by B Cell Receptors. Ozawa T, Fujii K, Sudo T, Doi Y, Nakai R, Shingai Y, Ueda T, Baba Y, Hosen N, Yokota T. J Immunol. 2022 Apr 15;208(8):1937-1946. 2) Inotuzumab ozogamicin and blinatumomab sequential therapy for relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. Ueda T, Fukushima K, Kusakabe S, Yoshida K, Suga M, Nakai R, Koike M, Hino A, Akuta K, Toda J, Nagate Y, Doi Y, Fujita J, Yokota T, Hosen N. Leuk Res Rep. 2022 Feb 15;17:100294. 3) Autonomous TGFβ signaling induces phenotypic variation in human acute myeloid leukemia. Shingai Y, Yokota T, Okuzaki D, Sudo T, Ishibashi T, Doi Y, Ueda T, Ozawa T, Nakai R, Tanimura A, Ichii M, Shibayama H, Kanakura Y, Hosen N. Stem Cells. 2021 Jun;39(6):723-736. 4) Alectinib, an anaplastic lymphoma kinase (ALK) inhibitor, as a bridge to allogeneic stem cell transplantation in a patient with ALK-positive anaplastic large-cell lymphoma refractory to chemotherapy and brentuximab vedotin. Nakai R, Fukuhara S, Maeshima AM, Kim SW, Ito Y, Hatta S, Suzuki T, Yuda S, Makita S, Munakata W, Suzuki T, Maruyama D, Izutsu K. Clin Case Rep. 2019 Nov 15;7(12):2500-2504. 5) Endothelial Cell-Selective Adhesion Molecule Contributes to the Development of Definitive Hematopoiesis in the Fetal Liver. Ueda T, Yokota T, Okuzaki D, Uno Y, Mashimo T, Kubota Y, Sudo T, Ishibashi T, Shingai Y, Doi Y, Ozawa T, Nakai R, Tanimura A, Ichii M, Ezoe S, Shibayama H, Oritani K, Kanakura Y. Stem Cell Reports. 2019 Dec 10;13(6):992-1005. ID: 641
Therapy 1: preclinical developments Generation of a new neuronal model of Friedreich’s Ataxia and establishment of a drug screening strategy 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR7104, Université de Strasbourg, France; 2Institut NeuroMyoGene, UMR5261, INSERM U1315, Université Claude Bernard Lyon I Faculté de médecine, Lyon, France ID: 578
Therapy 1: preclinical developments Downregulation of miR-181a/b ameliorates the Leigh syndrome phenotype in Ndufs4 KO mice 1Telethon Institute of Genetics and Medicine, Telethon Foundation, Pozzuoli (NA), Italy; 2European School of Molecular Medicine (SEMM); 3Institute for Genetic and Biomedical Research (IRGB), National Research Council (CNR), Milan, Italy; 4Ecosustainable Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Naples, Italy; 5Institute of Biochemistry and Cellular Biology (IBBC), National Research Council (CNR), Monterotondo (RM), Italy; 6Dep. of Precision Medicine, University of Campania "L. Vanvitelli", Caserta, Italy; 7Dep. of Translational Medicine, University of Naples "Federico II", Naples, Italy Bibliography
1) Indrieri A, Carrella S, Romano A, Spaziano A, Marrocco E, Fernandez-Vizarra E, Barbato S, Pizzo M, Ezhova Y, Golia FM, Ciampi L, Tammaro R, Henao-Mejia J, Williams A, Flavell RA, De Leonibus E, Zeviani M, Surace EM, Banfi S, Franco B. miR-181a/b downregulation exerts a protective action on mitochondrial disease models. EMBO Mol Med. 2019 May;11(5):e8734. doi: 10.15252/emmm.201708734. PMID: 30979712; PMCID: PMC6505685. 2) Kruse SE, Watt WC, Marcinek DJ, Kapur RP, Schenkman KA, Palmiter RD. Mice with mitochondrial complex I deficiency develop a fatal encephalomyopathy. Cell Metab. 2008 Apr;7(4):312-20. doi: 10.1016/j.cmet.2008.02.004. PMID: 18396137; PMCID: PMC2593686. 3) Barbato A, Iuliano A, Volpe M, D'Alterio R, Brillante S, Massa F, De Cegli R, Carrella S, Salati M, Russo A, Russo G, Riccardo S, Cacchiarelli D, Capone M, Madonna G, Ascierto PA, Franco B, Indrieri A, Carotenuto P. Integrated Genomics Identifies miR-181/TFAM Pathway as a Critical Driver of Drug Resistance in Melanoma. Int J Mol Sci. 2021 Feb 11;22(4):1801. doi: 10.3390/ijms22041801. PMID: 33670365; PMCID: PMC7918089. 4) Carrella S, Indrieri A, Franco B, Banfi S. Mutation-Independent Therapies for Retinal Diseases: Focus on Gene-Based Approaches. Front Neurosci. 2020 Sep 24;14:588234. doi: 10.3389/fnins.2020.588234. PMID: 33071752; PMCID: PMC7541846. ID: 461
Therapy 1: preclinical developments Succinate does not increase reactive oxygen species generation in phosphorylating human mitochondria 1Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; 2Department of Anesthesiology, Tokyo Medical University, Tokyo, Japan; 3Abliva, AB, Lund, Sweden; 4Otorhinolaryngology Head and Neck Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden Bibliography
Ganetzky RD, Markhard AL, Yee I, Clever S, Cahill A, Shah H, Grabarek Z, To TL, Mootha VK. Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation. N Engl J Med. 2022;387(15):1395-403. ID: 555
Therapy 1: preclinical developments Disease modeling and drug screening of mitochondrial complex I disorders: From Podospora anserina to Human 1MITOVASC Institute, CNRS UMR 6015 INSERM U1083, Angers University - Angers (France); 2Pharmacology laboratory UR7296, Strasbourg University - Strasbourg (France); 3Côte d'Azur University, CNRS, Institute of Chemistry- Nice (France); 4IRCAN, UMR 7284 INSERM U1081/UCA - Nice (France); 5IBGC Institute, CNRS UMR 5095 - Bordeaux (France); 6Institute for Integrative Biology of the Cell I2BC, UMR9198, University of Paris-Saclay - Paris (France) ID: 469
Therapy 1: preclinical developments Nifuroxazide rescues deleterious effects of MICOS disassembly in disease models 1IRCAN, UMR 7284/INSERM U1081/UCA, Nice, France; 2Université Côte d’Azur, Centre Commun de Microscopie Appliquée, Nice, France; 3Université Côte d’Azur, Inserm U1065, C3M, Nice, France; 4Université Paris Saclay, CEA, CNRS, I2BC, Gif-sur-Yvette, France; 5Université Côte d’Azur, CNRS UMR 7272, ICN, Nice, France; 6Université Paris Descartes-Sorbonne Paris Cité, Inserm U1163, Imagine Institute, Paris, France; 7IBGC, UMR5095 CNRS, Bordeaux, France; 8CRBS, UR7296, Strasbourg, France; 9Université d'Angers, UMR CNRS 6015 – INSERM U1083, Angers, France Bibliography
1.Genin* EC, Bannwarth* S, Ropert B, Lespinasse F, Mauri-Crouzet A, Augé G, Fragaki K, Cochaud C, Donnarumma E, Lacas-Gervais S, Wai T, Paquis-Flucklinger V. CHCHD10 and SLP2 control the stability of the PHB complex: a key factor for motor neuron viability. Brain. 2022 Jun 3:awac197. (*co-first authors). doi: 10.1093/brain/awac197. Epub ahead of print. PMID: 35656794. 2.Baek M, Choe Y-J, Bannwarth S, Kim J, Maitra S, Dorn II GW, Taylor JP, Paquis-Flucklinger V, Kim NC. Dominant toxicity of ALS–FTD-associated CHCHD10S59L is mediated by TDP-43 and PINK1. Nat Com, 2021; 74 :20-38. 3. Genin EC, Madji Hounoum B, Bannwarth S, Fragaki K, Lacas-Gervais S, Mauri-Crouzet A, Lespinasse F, Neveu J, Ropert B, Augé G, Cochaud C, Lefebvre-Omar C, Bigou S, Chiot A, Mochel F, Boillée S, Lobsiger CS, Bohl D, Ricci JE, Paquis-Flucklinger. Mitochondrial defect in muscle precedes neuromuscular junction degradation and motor neuron death in CHCHD10S59L/+ mouse. Acta Neuropathol, 2019; 138:123-145. ID: 420
Therapy 1: preclinical developments Lithospermum erythrorhizon complexs extract prevents dexamethasone-induced muscle atrophy in mice Korea Food Research Institute, Korea, Republic of (South Korea) Bibliography
Fuzhuan brick tea extract prevents diet-induced obesity via stimulation of fat browning in mice. Food Chem. 2022 May 30;377:132006 ID: 104
Therapy 1: preclinical developments Myocardial regeneration therapy using human cardiosphere-derived cells with activated mitochondria 1Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; 3Faculty of Engineering, Hokkaido University, Sapporo, Japan; 4Fusion Oriented REsearch for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan ID: 464
Therapy 1: preclinical developments Quinone compounds in primary mitochondrial disease: in vitro characterization of NQO1-mediated NAD+/NADH modulation 1Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden; 2Isomerase Therapeutics Ltd, Chesterford Research Park, Cambridge, UK; 3Abliva AB, Lund, Sweden Bibliography
Åsander Frostner E, Simón Serrano S, Chamkha I, Donnelly E, Elmér E, Hansson MJ (2022) Towards a treatment for mitochondrial disease: current compounds in clinical development. https://doi.org/10.26124/mitofit:2022-0014 — 2022-06-28 published in Bioenerg Commun 2022.4. ID: 248
Therapy 1: preclinical developments Metformin in mitochondrial disease patients cardiac cells University of Eastern Finland, Finland Bibliography
Ryytty S, Modi SR, Naumenko N, et al. Varied Responses to a High m.3243A>G Mutation Load and Respiratory Chain Dysfunction in Patient-Derived Cardiomyocytes. Cells. 2022;11(16):2593. Published 2022 Aug 19. doi:10.3390/cells11162593 ID: 386
Therapy 2: clinical trials Mavodelpar clinical development program in adult patients with primary mitochondrial myopathy (PMM): results from Phase 1b study and design of ongoing pivotal study (STRIDE). 1Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK; 2NHS Highly Specialised Service for Rare Mitochondrial Disorders, Queen Square Centre for Neuromuscular Diseases, The National Hospital for Neurology and Neurosurgery, London, UK; 3Wellcome Centre for Mitochondrial Research, Newcastle University, UK; 4NIHR Newcastle Biomedical Research Centre, Newcastle University, UK; 5Paramstat Ltd., UK; 6Reneo Pharma Ltd., UK; 7Reneo Pharmaceuticals Inc., USA; 8Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Italy; 9Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA ID: 509
Therapy 2: clinical trials Rationale and design of a clinical phase 2a study to evaluate the safety and efficiency of OMT-28 in primary mitochondrial disease 1OMEICOS Therapeutics GmbH, Germany; 2University of Alberta, Canada; 3Max-Delbrueck Center for Molecular Medicine, Germany ID: 101
Therapy 2: clinical trials Treatment with lenadogene nolparvovec gene therapy results in sustained visual improvement in m.11778G>A MT-ND4-LHON patients: the RESTORE study 1Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 2Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, GA, USA; 3IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 4Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 5Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 6Department of Neurology, Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany; 7Doheny Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 8GenSight Biologics, Paris, France; 9Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France Bibliography
Newman NJ, Yu-Wai-Man P, Subramanian PS, Moster ML, Wang AG, Donahue SP, Leroy BP, Carelli V, Biousse V, Vignal-Clermont C, Sergott RC, Sadun AA, Fernández GR, Chwalisz BK, Banik R, Bazin F, Roux M, Cox ED, Taiel M, Sahel JA; LHON REFLECT Study Group. Randomized trial of bilateral gene therapy injection for m.11778G > A MT-ND4 Leber optic neuropathy. Brain. 2022 Nov 9:awac421. doi: 10.1093/brain/awac421. Epub ahead of print. PMID: 36350566. Chen BS, Holzinger E, Taiel M, Yu-Wai-Man P. The Impact of Leber Hereditary Optic Neuropathy on the Quality of Life of Patients and Their Relatives: A Qualitative Study. J Neuroophthalmol. 2022 Sep 1;42(3):316-322. doi: 10.1097/WNO.0000000000001564. Epub 2022 Apr 27. PMID: 35483081. Biousse V, Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Esposti S, La Morgia C, Priglinger C, Karanja R, Blouin L, Taiel M, Sahel JA; LHON Study Group. Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study. J Neuroophthalmol. 2021 Sep 1;41(3):309-315. doi: 10.1097/WNO.0000000000001367. PMID: 34415265; PMCID: PMC8366761. ID: 124
Therapy 2: clinical trials Current status of the phase 3 trial of dichloroacetate (DCA) for pyruvate dehydrogenase complex deficiency (PDCD) 1University of Florida, United States of America; 2Saol Therapeutics, United States of America ID: 272
Therapy 2: clinical trials Efficacy and safety of elamipretide in subjects with primary mitochondrial disease resulting from pathogenic nuclear DNA mutations (nPMD): phase 3 study design 1Massachusetts General Hospital, Harvard Medical School Boston, MA, United States of America; 2Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Italy ID: 354
Therapy 2: clinical trials Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing change in visual acuity categories according to mitochondrial DNA mutation and disease phase 1John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 2Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 3Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; 4Institute of Ophthalmology, University College London, London, United Kingdom; 5IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 6Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 7Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 8The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; 9Chiesi Farmaceutici S.p.A., Parma, Italy; 10German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 12Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany ID: 352
Therapy 2: clinical trials Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing change in visual acuity over time according to mitochondrial DNA mutation and disease phase 1Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 2John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 3Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 4Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; 5Institute of Ophthalmology, University College London, London, United Kingdom; 6IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 7Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 8The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; 9Chiesi Farmaceutici S.p.A., Parma, Italy; 10German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 12Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany ID: 220
Therapy 2: clinical trials Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing the impact of idebenone on rates of recovery and worsening of vision according to primary mitochondrial DNA mutation 1Moorfields Eye Hospital NHS Foundation Trust, United Kingdom; 2Institute of Ophthalmology, University College London, London, United Kingdom; 3The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; 4John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 5Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 6Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 7IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 8Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 9Chiesi Farmaceutici S.p.A., Parma, Italy; 10German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 12Department of Neurology, Friedrich‑Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany ID: 330
Therapy 2: clinical trials Enzyme replacement strategy by transplantation in MNGIE: lessons from the updated Bologna case series 1IRCCS Istituto Scienze Neurologiche di Bologna, Italy; 2IRCCS Policlinico Sant’Orsola-Malpighi di Bologna, Bologna, Italy; 3Department of Clinical and experimental Medicine, University of Messina, Messina, Italy; 4Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena; 5Institute of Neurology, University of Verona, Verona, Italy; 6Center for Neuromuscular Diseases, Unit of Neurology, ASST "Spedali Civili", Brescia, Italy; 7Department of Medico-Surgical Sciences and Biotechnologies, University ‘La Sapienza’, Roma, Italy; 8Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, Italy Bibliography
•D'Angelo R, Rinaldi R, Carelli V, et al. ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy. Neurol Sci. 2016; 37:1149-1151 •De Giorgio R, Pironi L, Rinaldi R, Boschetti E, Caporali L, Capristo M, Casali C, Cenacchi G, Contin M, D'Angelo R, et al. Liver transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Ann Neurol. 2016;80:448-455 •D'Angelo R, Rinaldi R, Pironi L, et al. Liver transplant reverses biochemical imbalance in mitochondrial neurogastrointestinal encephalomyopathy. Mitochondrion. 2017;34:101-102 •Gramegna LL, Pisano A, Testa C, Manners DN, D'Angelo R, et al. Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy. AJNR Am J Neuroradiol. 2018; 39:427-434 •D'Angelo R, Boschetti E, Amore G et al. Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications. J Neurol. 2020;267:3702-3710 •Hirano M, Carelli V, De Giorgio R, Pironi L, Accarino A, Cenacchi G, D'Alessandro R, Filosto M, Martí R, Nonino F, Pinna AD, Baldin E, Bax BE, Bolletta A, Bolletta R, Boschetti E, Cescon M, D'Angelo R, et al. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.J Inherit Metab Dis. 2021; 44:376-387 •Boschetti E, D'Angelo R, Tardio ML, et al. Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy. Am J Physiol Gastrointest Liver Physiol. 2021; 320:G768-G779 •Boschetti E, Caporali L, D'Angelo R, et al. Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant. Int J Mol Sci. 2022; 23:8792 ID: 517
mtDNA maintenance and expression Developing mouse models to investigate the molecular mechanisms of POLG-related diseases 1Venetian Institute of Molecular Medicine, Padova; 2Department of Neuroscience, University of Padova; 3Department of Biomedical Sciences, University of Padova; 4Dept. Medical Chemistry & Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg; 5Mitochondrial Biology Unit, MRC/University of Cambridge, Cambridge, UK ID: 361
Therapy 2: clinical trials Long-term efficacy of idebenone in patients with LHON in the LEROS study: Analyzing the impact of idebenone on rates of recovery and worsening of vision according to disease phase 1Chiesi Farmaceutici S.p.A., Parma, Italy; 2John van Geest Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; 3Cambridge Eye Unit, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 4Moorfields Eye Hospital NHS Foundation Trust, United Kingdom; 5Institute of Ophthalmology, University College London, London, United Kingdom; 6IRCCS Istituto di Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 7Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 8Department of Ophthalmology, Medical University of Vienna, Vienna, Austria; 9The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, United Kingdom; 10German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; 12Department of Neurology, Friedrich Baur Institute, University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany ID: 122
Therapy 1: preclinical developments Validation of drug delivery and functional activation to mitochondria in skeletal muscle cell 1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; 2Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 3Faculty of Engineering, Hokkaido University, Sapporo, Japan; 4Fusion Oriented research for disruptive Science and Technology (FOREST) Program, Japan Science and Technology Agency (JST) Japan, Saitama, Japan ID: 132
mtDNA maintenance and expression Novel approaches to modulate mutant mitochondrial DNA in patient-derived induced-pluripotent stem cells 1Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; 2Department of Molecular Genetics, University of Toronto, Toronto, Canada; 3Department of Psychiatry, University of Toronto, Toronto, ON, Canada Bibliography
Bodenstein DF, Kim HK, Brown NC, Navaid B, Young LT, Andreazza AC. Mitochondrial DNA content and oxidation in bipolar disorder and its role across brain regions. NPJ Schizophr. 2019 Dec 4;5(1):21. doi: 10.1038/s41537-019-0089-5. PMID: 31797868; PMCID: PMC6892804. Choi J, Bodenstein DF, Geraci J, Andreazza AC. Evaluation of postmortem microarray data in bipolar disorder using traditional data comparison and artificial intelligence reveals novel gene targets. J Psychiatr Res. 2021 Oct;142:328-336. doi: 10.1016/j.jpsychires.2021.08.011. Epub 2021 Aug 15. PMID: 34419753. Cadoná FC, de Souza DV, Fontana T, Bodenstein DF, Ramos AP, Sagrillo MR, Salvador M, Mota K, Davidson CB, Ribeiro EE, Andreazza AC, Machado AK. Açaí (Euterpe oleracea Mart.) as a Potential Anti-neuroinflammatory Agent: NLRP3 Priming and Activating Signal Pathway Modulation. Mol Neurobiol. 2021 Sep;58(9):4460-4476. doi: 10.1007/s12035-021-02394-x. Epub 2021 May 22. PMID: 34021869. de Souza DV, Pappis L, Bandeira TT, Sangoi GG, Fontana T, Rissi VB, Sagrillo MR, Duarte MM, Duarte T, Bodenstein DF, Andreazza AC, Cruz IBMD, Ribeiro EE, Antoniazzi A, Ourique AF, Machado AK. Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells. Nutr Neurosci. 2022 Jun;25(6):1188-1199. doi: 10.1080/1028415X.2020.1842044. Epub 2020 Nov 10. PMID: 33170113. ID: 309
mtDNA maintenance and expression Evaluation of mtDNA copy number assessment in patients with suspected mitochondrial disease 1NHS Highly Specialised Services for Rare Mitochondrial Disorders, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 2Oxford Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 3Department of Neurology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 4Department of Neurology, Gregorio Marañón University Hospital, Madrid, Spain; 5Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, UK Bibliography
PMID: 36513735 PMID: 35141356 PMID: 35024855 ID: 382
Therapy 1: preclinical developments Hepatoencephalopathy due to GFM1 mutations: generation of a mouse model and preclinical study of an AAV-based gene therapy for the disease 1Research Group on Neuromuscular and Mitochondrial Diseases, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona - Barcelona (Spain); 2Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III - Madrid (Spain); 3Pathology Department, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona - Barcelona (Spain); 4Programa de Terapia Génica y Regulación de la Expresión Génica, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra - Pamplona (Spain); 5Instituto de Investigación Sanitaria de Navarra, IdiSNA - Pamplona (Spain) Bibliography
Molina-Berenguer M, Vila-Julià F, Pérez-Ramos S, Salcedo-Allende MT, Cámara Y, Torres-Torronteras J, Martí R. Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to Gfm1 mutations. FASEB J. 2022 Jan;36(1):e22091. doi: 10.1096/fj.202100819RRR. PMID: 34919756. ID: 549
Therapy 1: preclinical developments Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior 1Université Paris Cité, NeuroDiderot, Inserm, F-75019 Paris, France; 2Neonatal Research Group, Health Research Institute La Fe, 46026 Valencia, Spain; 3Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; 4Université Paris Cité, Platform of Cellular and Molecular Imaging, US25 Inserm, UAR3612 CNRS, 75006 Paris, France; 5Université de Paris, UMR-S 1144 Inserm, 75006 Paris, France Bibliography
1.Hélène Cwerman-Thibault, Christophe Lechauve, Vassilissa Malko-Baverel, Sébastien Augustin, Gwendoline Le Guilloux, Élodie Reboussin, Julie Degardin-Chicaud, Manuel Simonutti, Thomas Debeir, Marisol Corral-Debrinski. Neuroglobin effectively halts vision loss in Harlequin mice at an advanced stage of optic nerve degeneration. Neurobiology of Disease, 2021. doi.org/10.1016/j.nbd.2021.105483. 2.Hélène Cwerman-Thibault, Vassilissa Malko-Baverel, Gwendoline Le Guilloux, Isabel Torres-Cuevas, Bruno Saubaméa, Edward Ratcliffe, Djmila Mouri, Virginie Mignon, Odile Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski. Harlequin mice exhibit cognitive impairment, severe loss of Purkinje cells and a compromised bioenergetic status due to the absence of Apoptosis Inducing Factor. Brain Pathology (In submission). 3.Hélène Cwerman-Thibault, Vassilissa Malko-Baverel, Gwendoline Le Guilloux, Edward Ratcliffe, Djmila Mouri, Isabel Torres-Cuevas, Ivan Millán, Virginie Mignon, Bruno Saubaméa, Odile Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski. Neuroglobin overexpression in cerebellar neurons of Harlequin mice improves mitochondrial homeostasis and reduces ataxic behavior. (In submission) ID: 1411
mtDNA maintenance and expression Guanylate kinase 1 deficiency: a novel and potentially treatable form of mitochondrial DNA depletion/deletions syndrome 1Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; 2Seattle Children’s Hospital, Seattle, WA, USA; 3Section of Inborn Errors of Metabolism-IBC. Department of Biochemistry and Molecular Genetics. Hospital Clinic de Barcelona-IDIBAPS, Barcelona.; 4Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona; 5Muscle Research and Mitochondrial Function Lab, Cellex - IDIBAPS. Faculty of Medicine and Health Science - University of Barcelona (UB), Barcelona.; 6Department of Internal Medicine, Hospital Clínic of Barcelona.; 7Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain.; 8Department of Genome Sciences, University of Washington, Seattle, WA, U.S.A. Bibliography
1DiMauro, S., Schon, E. A., Carelli, V. & Hirano, M. The clinical maze of mitochondrial neurology. Nat Rev Neurol 9, 429-444, doi:10.1038/nrneurol.2013.126 (2013). 2Lopez-Gomez, C., Camara, Y., Hirano, M., Marti, R. & nd, E. W. P. 232nd ENMC international workshop: Recommendations for treatment of mitochondrial DNA maintenance disorders. 16 - 18 June 2017, Heemskerk, The Netherlands. Neuromuscul Disord 32, 609-620, doi:10.1016/j.nmd.2022.05.008 (2022). 3Lane, A. N. & Fan, T. W. Regulation of mammalian nucleotide metabolism and biosynthesis. Nucleic Acids Res 43, 2466-2485, doi:10.1093/nar/gkv047 (2015). 4Saada, A., Shaag, A., Mandel, H., Nevo, Y., Eriksson, S. & Elpeleg, O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29, 342-344, doi:10.1038/ng751 (2001). 5Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S. & Cohen, N. The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29, 337-341, doi:10.1038/ng746 (2001). 6Ostergaard, E., Christensen, E., Kristensen, E., Mogensen, B., Duno, M., Shoubridge, E. A. & Wibrand, F. Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet 81, 383-387, doi:10.1086/519222 (2007). 7Besse, A., Wu, P., Bruni, F., Donti, T., Graham, B. H., Craigen, W. J., McFarland, R., Moretti, P., Lalani, S., Scott, K. L., Taylor, R. W. & Bonnen, P. E. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. Cell Metab 21, 417-427, doi:10.1016/j.cmet.2015.02.008 (2015). 8Sommerville, E. W., Dalla Rosa, I., Rosenberg, M. M., Bruni, F., Thompson, K., Rocha, M., Blakely, E. L., He, L., Falkous, G., Schaefer, A. M., Yu-Wai-Man, P., Chinnery, P. F., Hedstrom, L., Spinazzola, A., Taylor, R. W. & Gorman, G. S. Identification of a novel heterozygous guanosine monophosphate reductase (GMPR) variant in a patient with a late-onset disorder of mitochondrial DNA maintenance. Clin Genet 97, 276-286, doi:10.1111/cge.13652 (2020). 9Shintaku, J., Pernice, W. M., Eyaid, W., Gc, J. B., Brown, Z. P., Juanola-Falgarona, M., Torres-Torronteras, J., Sommerville, E. W., Hellebrekers, D. M., Blakely, E. L., Donaldson, A., van de Laar, I., Leu, C. S., Marti, R., Frank, J., Tanji, K., Koolen, D. A., Rodenburg, R. J., Chinnery, P. F., Smeets, H. J. M., Gorman, G. S., Bonnen, P. E., Taylor, R. W. & Hirano, M. RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J Clin Invest 132, doi:10.1172/JCI145660 (2022). 10Bourdon, A., Minai, L., Serre, V., Jais, J. P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H., Nakamura, Y., Munnich, A. & Rotig, A. Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet 39, 776-780, doi:10.1038/ng2040 (2007). 11Khan, N., Shah, P. P., Ban, D., Trigo-Mourino, P., Carneiro, M. G., DeLeeuw, L., Dean, W. L., Trent, J. O., Beverly, L. J., Konrad, M., Lee, D. & Sabo, T. M. Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer. J Biol Chem 294, 11920-11933, doi:10.1074/jbc.RA119.009251 (2019). 12Li, Y., Zhang, Y. & Yan, H. Kinetic and thermodynamic characterizations of yeast guanylate kinase. J Biol Chem 271, 28038-28044, doi:10.1074/jbc.271.45.28038 (1996). 13Agarwal, K. C., Miech, R. P. & Parks, R. E., Jr. Guanylate kinases from human erythrocytes, hog brain, and rat liver. Methods Enzymol 51, 483-490, doi:10.1016/s0076-6879(78)51066-5 (1978). 14Dummer, R., Duvic, M., Scarisbrick, J., Olsen, E. A., Rozati, S., Eggmann, N., Goldinger, S. M., Hutchinson, K., Geskin, L., Illidge, T. M., Giuliano, E., Elder, J. & Kim, Y. H. Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sezary syndrome). Ann Oncol 25, 1807-1812, doi:10.1093/annonc/mdu231 (2014). ID: 1524
mtDNA maintenance and expression Mechanisms of mtDNA maintenance and segregation in the female germline 1Karolinska Institutet, Stockholm, Sweden; 2MRC Mitochondrial Biology Unit, Cambridge, United Kingdom; 3Department of Clinical Neurosciences, University of Cambridge, United Kingdom ID: 1127
mtDNA maintenance and expression Processing of mitochondrial RNA in health and disease: the role of FASTKD5. 1The Neuro & McGill University, Montreal, Quebec, Canada; 2Dell School of Medicine, University of Texas at Austin, Austin, TX, USA Bibliography
1.Arguello T, Peralta S, Antonicka H, Gaidosh G, Diaz F, Tu YT, Garcia S, Shiekhattar R, Barrientos A, Moraes CT. (2021) ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly. Cell Rep. 2021 Dec 21;37(12):110139. doi: 10.1016/j.celrep.2021.110139. 2.Go CD, Knight JDR, Rajasekharan A, Rathod B, Hesketh GG, Abe KT, Youn JY, Samavarchi-Tehrani P, Zhang H, Zhu LY, Popiel E, Lambert JP, Coyaud É, Cheung SWT, Rajendran D, Wong CJ, Antonicka H, Pelletier L, Palazzo AF, Shoubridge EA, Raught B, Gingras AC. (2021) A proximity-dependent biotinylation map of a human cell. Nature. 2021 Jul;595(7865):120-124. doi: 10.1038/s41586-021-03592-2. 3.Antonicka H, Lin ZY, Janer A, Aaltonen MJ, Weraarpachai W, Gingras AC, Shoubridge EA. (2020) A High-Density Human Mitochondrial Proximity Interaction Network. Cell Metab. 2020 Sep 1;32(3):479-497.e9. doi: 10.1016/j.cmet.2020.07.017. 4.Maiti P, Antonicka H, Gingras AC, Shoubridge EA, Barrientos A. (2020) Human GTPBP5 (MTG2) fuels mitoribosome large subunit maturation by facilitating 16S rRNA methylation. Nucleic Acids Res. 2020 Aug 20;48(14):7924-7943. doi: 10.1093/nar/gkaa592. 5.Antonicka H, Choquet K, Lin ZY, Gingras AC, Kleinman CL, Shoubridge EA. (2017) A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Rep. 2017 Jan;18(1):28-38. doi: 10.15252/embr.201643391. ID: 1116
mtDNA maintenance and expression The human Mitochondrial mRNA Structurome reveals Mechanisms of Gene Expression in Physiology and Pathology 1University of Miami, United States of America; 2Harvard Medical School, United States of America Bibliography
1- Structural basis of LRPPRC-SLIRP-1 dependent translation by the mitoribosome. Vivek Singh, J. Conor Moran, Yuzuru Itoh, Iliana C. Soto, Flavia Fontanesi, Mary Couvillion, Martijn A. Huynen4, Stirling Churchman, Antoni Barrientos*, Alexey Amunts*. Nat Struct Mol Bill. 2023 (in press) 2-Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors. Timón-Gómez A, Scharr AL, Wong NY, Ni E, Roy A, Liu M, Chau J, Lampert JL, Hireed H, Kim NS, Jan M, Gupta AR, Day RW, Gardner JM, Wilson RJA, Barrientos A, Chang AJ. Elife. 2022 Oct 18;11:e78915. doi: 10.7554/eLife.78915. 2- Coordination of metal center biogenesis in human cytochrome c oxidase. Nývltová E, Dietz JV, Seravalli J, Khalimonchuk O, Barrientos A. Nat Commun. 2022 Jun 24;13(1):3615. doi: 10.1038/s41467-022-31413-1. ID: 1693
Late breaking news Host-microbiome co-adaptation to severe nutritional challenge 1Department of Biomolecular Sciences, Weizmann Institute of Science, Israel; 2Life Sciences Core Facilities, Weizmann Institute of Science, Israel ID: 1686
Late breaking news The heme exporter FLVCR1a regulates ER-mitochondria membranes tethering and mitochondrial calcium handling 1University of Turin, Department of Molecular Biotechnology and Health Sciences; 2Department of Pediatrics, University of California San Francisco, San Francisco, United States; 3Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy; 4Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; 5Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile; 6Leibniz Institute of Analytical Sciences, ISAS, Dortmund, Germany; 7Department of Oncology, University of Torino, Italy; 8Department of Pediatric Neurology, Developmental Neurology, and Social Pediatrics, Center for Neuromuscular Disorders in Children and Adolescents, University of Duisburg-Essen, Essen, Germany ID: 1512
Therapy 1: preclinical developments Genetic variants impact on NQO1 expression and activity driving efficacy of idebenone treatment in Leber’s hereditary optic neuropathy cell models 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy.; 3Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 4Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. ID: 1292
Therapy 1: preclinical developments Peptide mimetic molecules as potential therapeutic agents against diseases related to mt-tRNA point mutations. 1Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Italy; 2Department of Biochemical Sciences "A. Rossi Fanelli, Sapienza University of Rome, Italy; 3Institute of Molecular Biology and Pathology (IBPM), National Research Council (CNR) of Italy Bibliography
Perli E, Pisano A, Pignataro MG, Campese AF, Pelullo M, Genovese I, de Turris V, Ghelli AM, Cerbelli B, Giordano C, Colotti G, Morea V, d'Amati G. Exogenous peptides are able to penetrate human cell and mitochondrial membranes, stabilize mitochondrial tRNA structures, and rescue severe mitochondrial defects. FASEB J. 2020 Jun;34(6):7675-7686. doi: 10.1096/fj.201903270R Italian Patent n.102021000032930 THERAPEUTICAL PEPTIDOMIMETIC Inventors: Giulia d’Amati, Veronica Morea, Annalinda Pisano, Elena Perli, Maria Gemma Pignataro International application No. PCT/IB2022/062354 ID: 1152
Therapy 1: preclinical developments The mitoDdCBE system as a mitochondrial gene therapy approach 1University of Miami, United States of America; 2Max Planck Institute of Biochemistry, Germany; 3Broad Institute, Harvard University, and HHMI, United States of America Bibliography
Mitochondrial genome engineering coming-of-age. Barrera-Paez et al. Trends Genet. 2022, May 19. PMID: 35599021. Mitochondrial gene editing. Shoop et al (Barrera-Paez as third author). Nat Rev Methods Primers. 2023, in press (March 16). ID: 1355
Therapy 2: clinical trials Niacin treatment improves metabolic changes in early-stage mitochondrial myopathy 1Research Program for Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 3Department of Neurosciences, Helsinki University Hospital, Helsinki, Finland; 4Department of Clinical Physiology and Nuclear Medicine, Laboratory of Clinical Physiology, Helsinki University Hospital, Helsinki, Finland; 5HUS Diagnostic Center, Radiology, Helsinki University and Helsinki University Hospital, Helsinki, Finland; 6Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; 7Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 8Healthy Weight Hub, Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 9Helsinki University Hospital Diagnostic Centre, Helsinki, Finland Bibliography
Eija Pirinen, Mari Auranen, Nahid A. Khan, Virginia Brilhante, Niina Urho, Alberto Pessia, Antti Hakkarainen, Juho Kuula, Ulla Heinonen, Mark S. Schmidt, Kimmo Haimilahti, Päivi Piirilä, Nina Lundbom, Marja-Riitta Taskinen, Charles Brenner, Vidya Velagapudi, Kirsi H. Pietiläinen, Anu Suomalainen. Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab 2020;31(6):1078-1090.e5. ID: 1573
Therapy 2: clinical trials PHEMI: Phenylbutyrate Therapy in Mitochondrial Diseases with lactic acidosis: an open label clinical trial in MELAS and PDH deficiency patients. 1Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Experimental Neuroscience, Unit of Medical Genetics and Neurogenetics, Milan, Italy; 2Fondazione IRCCS Istituto Neurologico Carlo Besta, Department of Pediatric Neurosciences, Milan, Italy; 3Neurological Institute, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Bibliography
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis. Ferriero R, Manco G, Lamantea E, Nusco E, Ferrante MI, Sordino P, Stacpoole PW, Lee B, Zeviani M, Brunetti-Pierri N. Sci Transl Med. 2013 Mar 6;5(175):175ra31. doi: 10.1126/scitranslmed.3004986. PMID: 23467562 ID: 1102
Therapy 2: clinical trials Use of lenadogene nolparvovec gene therapy for Leber hereditary optic neuropathy in early access programs 1IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 2Department of Neuro Ophthalmology and Emergencies, Rothschild Foundation Hospital, Paris, France; 3Centre Hospitalier National d’Ophtalmologie des Quinze Vingts, Paris, France; 4Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University, Philadelphia, PA, USA; 5Department of Ophthalmology, Neurology, and Pediatrics, Vanderbilt University, and Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA; 6Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 7Institut de Génétique Médicale d’Alsace, CHU de Strasbourg, Strasbourg, France; 8Friedrich-Baur-Institute, University Hospital, Ludwig-Maximilians-University, Munich, Germany; 9University Hospital, Ludwig-Maximilians-University, Munich, Germany; 10Service Explorations de la Vision et Neuro-Ophtalmologie, CHU de Lille, Lille, France; 11Service d'Ophtalmologie, CHU de Rennes, Rennes, France; 12Service d'Ophtalmologie, CHU de Bordeaux, Groupe Hospitalier Pellegrin, Bordeaux, France; 13Service d'Ophtalmologie, CHU de Nantes, Nantes, France; 14Service de Neuro-Cognition et Neuro-Ophtalmologie, CHU de Lyon, Lyon, France; 15Service d'Ophtalmologie, Centre Hospitalier de Valence, Valence, France; 16Service d'Ophtalmologie, CHU de Caen, Caen, France; 17Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA; 18Retina Consultants, P.C, Hartford, Connecticut, USA; 19Service d'Ophtalmologie, Hôpital Ophtalmique Jules-Gonin, Lausanne, Switzerland; 20Centre Hospitalier de Wallonie Picarde, Tournai, Belgium; 21GenSight Biologics, Paris, France; 22Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France; 23Department of Biomedical and Neuromotor Sciences, DIBINEM, Bologna, Italy Bibliography
Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, La Morgia C, Karanjia R, Taiel M, Blouin L, Burguière P, Smits G, Chevalier C, Masonson H, Salermo Y, Katz B, Picaud S, Calkins DJ, Sahel JA. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med. 2020 Dec 9;12(573):eaaz7423. doi: 10.1126/scitranslmed.aaz7423. PMID: 33298565. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. PMID: 34108929; PMCID: PMC8181419. Biousse V, Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Esposti S, La Morgia C, Priglinger C, Karanja R, Blouin L, Taiel M, Sahel JA; LHON Study Group. Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study. J Neuroophthalmol. 2021 Sep 1;41(3):309-315. doi: 10.1097/WNO.0000000000001367. PMID: 34415265; PMCID: PMC8366761. ID: 1453
Therapy 3: reproductive options and mtDNA editing MitoCRISPR/Cas9 shifts mtDNA heteroplasmy not as effective as other site-specific nucleases. 1Novosibirsk State University, Novosibirsk, Russia; 2Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia; 3Skolkovo Institute of Science and Technology, Moscow, Russia Bibliography
1.Tanaka, M.; Borgeld, H.-J.; Zhang, J.; Muramatsu, S.; Gong, J.-S.; Yoneda, M.; Maruyama, W.; Naoi, M.; Ibi, T.; Sahashi, K.; et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J. Biomed. Sci. 2002, 9, 534–41. https://doi.org/10.1159/000064726. 2. Zakirova, E.G.; Vyatkin, Y.V.; Verechshagina, N.A.; Muzyka, V.V.; Mazunin, I.O.; Orishchenko, K.E. Study of the effect of the introduction of mitochondrial import determinants into the gRNA structure on the activity of the gRNA/SpCas9 complex in vitro.Vavilov Journal of Genetics and Breeding 2020, 24(5):512-518. https://doi.org/10.18699/VJ20.643. 3.Silva-Pinheiro, P., Minczuk, M. The potential of mitochondrial genome engineering. Nat Rev Genet 23, 199–214 (2022). https://doi.org/10.1038/s41576-021-00432-x. 4. Zakirova, E.G.; Muzyka, V.V.; Mazunin, I.O.; Orishchenko, K.E. Natural and Artificial Mechanisms of Mitochondrial Genome Elimination. Life 2021, 11, 76. https://doi.org/10.3390/life11020076. ID: 1271
Therapy 3: reproductive options and mtDNA editing Prenatal diagnostics for a family with 13513G>A mtDNA mutation associated with Leigh Syndrome 1Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, United States of America; 2Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health and Science University, United States of America ID: 1155
Therapy 3: reproductive options and mtDNA editing Specific elimination of m.3243A>G mutant mitochondria DNA using mitoARCUS 1Precision BioSciences - Durham, NC, United States of America; 2University of Miami - Miami, FL, United States of America Bibliography
Shoop WK, Gorsuch CL, Bacman SR, Moraes CT. Precise and simultaneous quantification of mitochondrial DNA heteroplasmy and copy number by digital PCR. J Biol Chem. 2022;298(11):102574. doi:10.1016/j.jbc.2022.102574 ID: 2103
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Identification of autophagy as a functional target suitable for the pharmacological treatment of MPAN in vitro 1Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 2Protein Expression and Purification Facility, Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 3Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy; 4Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 5Bavarian NMR Centre, Department of Bioscience, School of Natural Sciences, Technical University of Munich, 85747 Garching, Germany; 6Molecular Cell Biology Section, Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 7Expertise Center Movement Disorders Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 8Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; 9Alembic, Experimental Imaging Center, IRCCS San Raffaele Hospital, 20132 Milan, Italy; 10Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU), 80336 Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; 12German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; 13Institute of Human Genetics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany ID: 246
Therapy 1: preclinical developments PPAR Gamma Agonist Pioglitazone restores Mitochondrial Quality Control in fibroblasts of PITRM1 deficient patients 1Fondazione IRCCS Istituto Neurologico Carlo Besta, Italy; 2Department of Biology, University of Padua, Italy; 3Department of Clinical Medicine, University of Bergen, Norway; 4Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel; 5Molecular Medicine, IRCCS Fondazione Stella Maris, Italy; 6Department of Biomedical Sciences, University of Padova, Italy; 7Department of Neurosciences, University of Padova, Italy ID: 169
Therapy 1: preclinical developments Mitochondrial derived vesicles retain membrane potential and contain a functional ATP synthase 1Hebrew university, Israel; 2Technion, Haifa, Israel; 3Weizmann Institute of Science, Rehovot, Israel; 4Kimron Veterinary Institute, Bet Dagan, Israel; 5Hadassah Medical Center and Faculty of Medicine, Hebrew University, Jerusalem Israel Bibliography
Weill U1, Yofe I1, Sass E2, Stynen B3, Davidi D4, Natarajan J5, Ben-Menachem R6, Avihou Z1, Goldman O1, Harpaz N1, Chuartzman S1, Kniazev K1, Knoblach B7, Laborenz J8, Boos F8, Kowarzyk J3, Ben-Dor S9, Zalckvar E1, Herrmann JM8, Rachubinski RA7, Pines O6, Rapaport D5, Michnick SW3, Levy ED2, Schuldiner M10. Genome-wide SWAp-Tag yeast libraries for proteome exploration. Nat Methods. 2018 Jul 9. doi: 10.1038/s41592-018-0044-9 Ben-Menachem R, Wang K, Marcu O, Yu Z, Lim TK, Lin Q, Schueler-Furman O, Pines O. Yeast aconitase mitochondrial import is modulated by interactions of its C and N terminal domains and Ssa1/2 (Hsp70). Scientific Reports volume 8, Article number: 5903(2018) Ben-Menachem R, Pines O. 2017. Detection of Dual Targeting and Dual Function of Mitochondrial Proteins in Yeast. Methods Mol Biol. 2017;1567:179-195 Ben-Menachem R, Tal M, Shadur T and Pines O. 2011. A third of the yeast mitochondrial proteome is dual localized: a question of evolution. Proteomics. 11(23):4468-76. Impact Factor-4.815. Ben-Menachem R, Regev-rudzki N and Pines O. 2011. The aconitase C-terminal domain is an independent dual targeting element. J Mol Biol. 409(2):113-23. Impact Factor-4.0. ID: 516
mtDNA maintenance and expression Metabolic modulation of mitochondrial DNA release in cellular models of Parkin-associated Parkinson’s disease 1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; 2Institute of Neurogenetics, University of Lübeck, Lübeck, Germany Bibliography
1. Parkin Deficiency Impairs Mitochondrial DNA Dynamics and Propagates Inflammation. Wasner, Kobi; Smajic, Semra; Ghelfi, Jenny; Delcambre, Sylvie; Prada-Medina, Cesar A.; Knappe, Evelyn; Arena, Giuseppe; Mulica, Patrycja; Agyeah, Gideon; Rakovic, Aleksandar; Boussaad, Ibrahim; Badanjak, Katja; Ohnmacht, Jochen; Gerardy, Jean-Jacques; Takanashi, Masashi; Trinh, Joanne; Mittelbronn, Michel; Hattori, Nobutaka; Klein, Christine; Antony, Paul; Seibler, Philip; Spielmann, Malte; Pereira, Sandro L.; Grünewald, Anne in Movement disorders : official journal of the Movement Disorder Society (2022) 2. Neurodegeneration and Neuroinflammation in Parkinson’s Disease: a Self-Sustained Loop Arena, Giuseppe; Sharma, K.; Agyeah, Gideon; Krüger, Rejko; Grünewald, Anne; Fitzgerald, J. C. in Current Neurology and Neuroscience Reports (2022), 22(8), 427440 ID: 327
Mitochondrial mechanisms in neurodegeneration and neurodevelopment ATP synthase c-subunit leak metabolism associated with abnormal mitophagic clearance 1University College London, United Kingdom; 2Yale University , USA ID: 362
Metabolic stress responses in mitochondrial diseases, ageing and cancer Investigating the role of mitochondrial regulators in sorafenib and lenvatinib resistance in HCC cell line 1Department of Pharmacological and Biomolecular Sciences - DiSFeB, University of Milan, Italy; 2Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy ID: 310
Mitochondrial mechanisms in neurodegeneration and neurodevelopment Glucose-derived glutamate drives neuronal differentiation 1Department of Pharmacological and Biomolecular Sciences -DiSFeB, Università degli Studi di Milano, Milan, Italy; 2Department of Medical Biotechnology and Translational Medicine - BIOMETRA, Università degli Studi di Milano, Milan, Italy; 3Institute of Neuroscience, IN-CNR, Milan, Italy; 4Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland; 5Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy. |
| 4:15pm - 6:15pm | Patients' session Location: Bologna Congress Center - Sala Europa Chairs: Kira Mann, Paula Morandi 16:15 – 16:35 Mitochondrial Diseases in childhood: hope for the future – Robert McFarland 16:35 – 16:55 Advances in clinical diagnosis and management of mitochondrial disorders, Holger Prokish 16:55 – 17:15 New therapies for mitochondrial diseases – an update, Carlo Viscomi 17:15 – 17:35 Gene therapy for mitochondrial optic neuropathies – an update, Patrick Yu Wai Man 17:35 – 18:05 Ask the Mito Doc. Discussion with patients and experts 18:05 – 18:15 Q&A |
| 8:00pm - 10:00pm | Conference Dinner Location: Palazzo Re Enzo |
| Date: Thursday, 15/June/2023 | |
| 8:00am - 5:30pm | Registration Desk Location: Bologna Congress Center |
| 9:00am - 10:40am | Session 5.1: Late breaking news session Location: Bologna Congress Center - Sala Europa Session Chair: Valeria Tiranti Session Chair: Valerio Carelli |
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ID: 689 Late breaking news Improving the diagnosis of mitochondrial disease with public funding for whole genome sequencing Neuroscience Research Australia Bibliography
(1). Davis RL, Kumar KR, Puttick C, Liang C, Ahmad KE, Edema-Hildebrand F, Park JS, Minoche AE, Gayevskiy V, Mallawaarachchi AC, Christodoulou J, Schofield D, Dinger ME, Cowley MJ, Sue CM. Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis. Neurology. 2022 Aug 16;99(7):e730-e742. Oral presentation
ID: 687 Late breaking news SLC25A38 is Necessary for Mitochondrial Pyridoxal 5’-Phosphate (PLP) Accumulation 1Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA; 2Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; 3David H. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; 4Department of Biology, MIT, Cambridge, MA, USA; 5Harvard-MIT MD/PhD Program, Boston, MA, USA; 6Whitehead Institute for Biomedical Research, Cambridge, MA, USA; 7Cancer Research, Massachusetts General Hospital, Boston MA, USA; 8Cutaneous Biology Research Center, Massachusetts General Hospital Department of Dermatology, Harvard Medical School, Boston, MA; 9Unafilliated; 10Harvard T.H. Chan School of Public Health, Boston, MA, USA; 11Dana-Farber Cancer Institute, Boston, MA, USA Bibliography
(article in revision at Nature Metabolism) Oral presentation
ID: 685 Late breaking news The transcriptional effects of thyroid hormone T3 on mitochondrial metabolism during neurodevelopment 1Section of Pharmacology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; 3Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy Bibliography
1.Lanni A, Moreno M, Goglia F. Mitochondrial Actions of Thyroid Hormone. In: Terjung R, ed. Comprehensive Physiology. 1st ed. Wiley; 2016:1591-1607. doi:10.1002/cphy.c150019 2.Bifari F, Dolci S, Bottani E, et al. Complete neural stem cell (NSC) neuronal differentiation requires a branched chain amino acids-induced persistent metabolic shift towards energy metabolism. Pharmacol Res. 2020;158. doi:10.1016/j.phrs.2020.104863 3.Knobloch M, Pilz GA, Ghesquière B, et al. A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity. Cell Rep. 2017;20(9):2144-2155. doi:https://doi.org/10.1016/j.celrep.2017.08.029 4.Brunetti D, Dykstra W, Le S, Zink A, Prigione A. Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases. Stem Cells. 2021;39(10):1289-1297. doi:10.1002/stem.3425 5.Schwartz CE, Stevenson RE. The MCT8 thyroid hormone transporter and Allan–Herndon–Dudley syndrome. Best Pract Res Clin Endocrinol Metab. 2007;21(2):307-321. doi:10.1016/j.beem.2007.03.009 6.Cantó C, Houtkooper RH, Pirinen E, et al. The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity. Cell Metab. 2012;15(6):838-847. doi:10.1016/j.cmet.2012.04.022 Oral presentation
ID: 681 Late breaking news Transplanting ipsc-derived mitochondria: a promising approach for treating mitochondrial optic neuropathies Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore 138673, Singapore Flash Talk
ID: 686 Late breaking news The heme exporter FLVCR1a regulates ER-mitochondria membranes tethering and mitochondrial calcium handling 1University of Turin, Department of Molecular Biotechnology and Health Sciences; 2Department of Pediatrics, University of California San Francisco, San Francisco, United States; 3Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy; 4Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France; 5Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile; 6Leibniz Institute of Analytical Sciences, ISAS, Dortmund, Germany; 7Department of Oncology, University of Torino, Italy; 8Department of Pediatric Neurology, Developmental Neurology, and Social Pediatrics, Center for Neuromuscular Disorders in Children and Adolescents, University of Duisburg-Essen, Essen, Germany Flash Talk
ID: 693 Late breaking news Host-microbiome co-adaptation to severe nutritional challenge 1Department of Biomolecular Sciences, Weizmann Institute of Science, Israel; 2Life Sciences Core Facilities, Weizmann Institute of Science, Israel Flash Talk
ID: 103 Mitochondrial mechanisms in neurodegeneration and neurodevelopment Identification of autophagy as a functional target suitable for the pharmacological treatment of MPAN in vitro 1Institute of Neurogenomics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 2Protein Expression and Purification Facility, Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 3Medical Genetics and Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy; 4Institute of Structural Biology, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; 5Bavarian NMR Centre, Department of Bioscience, School of Natural Sciences, Technical University of Munich, 85747 Garching, Germany; 6Molecular Cell Biology Section, Department of Biomedical Sciences of Cells & Systems, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 7Expertise Center Movement Disorders Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands; 8Department of Neurology and Epileptology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; 9Alembic, Experimental Imaging Center, IRCCS San Raffaele Hospital, 20132 Milan, Italy; 10Department of Neurology, Friedrich-Baur-Institute, University Hospital of the Ludwig-Maximilians-University (LMU), 80336 Munich, Germany; 11Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany; 12German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; 13Institute of Human Genetics, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany Remote connection - Oral Presentation
ID: 2106 Late breaking news Nuclear genetic control of mtDNA homeostasis revealed from >250,000 human genomes Broad Institute; Mass Gen Hospital, Harvard Medical School |
| 10:40am - 10:55am | Coffee Break Location: Bologna Congress Center |
| 10:55am - 12:10pm | Keynote Lectures: Carlos Moraes - Thomas Becker Location: Bologna Congress Center - Sala Europa Session Chair: Luigi Palmieri Session Chair: Nils-Göran Larsson |
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Invited
ID: 674 Invited Speakers Promises and Perils of mitochondrial DNA Gene Editing 1University of Miami, United States of America; 2Precision Biosciences, United States of America Bibliography
1- Mitochondrial genome engineering coming-of-age: Barrera-Paez JD, Moraes CT. Trends Genet. 2023 Jan;39(1):89. Invited
ID: 671 Invited Speakers Control of mitochondrial protein import University of Bonn, Germany |
| 12:10pm - 12:50pm | Closing Lecture: Anu Suomalainen Location: Bologna Congress Center - Sala Europa |
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Invited
ID: 704 Invited Speakers Quo vadis, mitochondrial medicine Helsinki-Finland |
| 12:50pm - 1:00pm | Announcement of Award Winners Location: Bologna Congress Center - Sala Europa |
| 1:00pm - 1:10pm | Presentation of the next Euromit Conference Location: Bologna Congress Center - Sala Europa |
| 1:30pm - 2:30pm | Lunch Location: Bologna Congress Center - Sala Europa |
| 2:30pm - 6:00pm | Satellite Symposium: Mitochondrial optic neuropathies, the tip of the mito-iceberg Location: Bologna Congress Center - Sala Europa To see the full programme of this Meeting, visit our website on this page. |