Time: Tuesday, 13/June/2023: 3:30pm - 4:30pm |
Location: Bologna Congress Center Address: Piazza della Costituzione, 4/a, Bologna (BO), Italy |
- 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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
n/a
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)
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.
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
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
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.
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
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/)
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
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
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.
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
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
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
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
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
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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
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
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
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
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.
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
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
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
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)
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.
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
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
Inflammation and Immunity as mitochondrial contributor to pathology
Concerted cell-specific neuronal programs drive neurodegeneration in Leigh Syndrome
Universitat Autònoma de Barcelona, Spain
* 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.
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
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.
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
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.
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
Inflammation and Immunity as mitochondrial contributor to pathology
MtDNA replication stress and innate immune signalling
Max Planck Institute for Biology of Ageing, Germany
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.
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
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.
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
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
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.
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
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.
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.
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.
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
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
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
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.
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
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
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.
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.
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
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
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.
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
Metabolic stress responses in mitochondrial diseases, ageing and cancer
Stress responses in a novel mitochondrial myopathy mouse model
Bogazici University, Turkey
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
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.
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,
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
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
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
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
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
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
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
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
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
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
- Tykocki T, Eltayeb M. Ten-year survival in glioblastoma. A systematic review. J Clin Neurosci. Published online 2018. doi:10.1016/j.jocn.2018.05.002
- Michaelsen SR, Christensen IJ, Grunnet K, et al. Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer. 2013;13(1):402. doi:10.1186/1471-2407-13-402
- Colwell N, Larion M, Giles AJ, et al. Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells. Neuro Oncol. 2017;19(7):887-896. doi:10.1093/neuonc/now258
- Aldape K, Brindle KM, Chesler L, et al. Challenges to curing primary brain tumors. Nat Rev Clin Oncol. 2019;16(8):509-520. doi:10.1038/s41571-019-0177-5
- Desai R, East DA, Hardy L, et al. Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Sci Adv. 2020;6(51). doi:10.1126/sciadv.abc9955
- Kim S, Koh H. Role of FOXO transcription factors in crosstalk between mitochondria and the nucleus. J Bioenerg Biomembr. 2017;49. doi:10.1007/s10863-017-9705-0
- Strobbe D, Sharma S, Campanella M. Links between mitochondrial retrograde response and mitophagy in pathogenic cell signaling. Cell Mol Life Sci. 2021. doi:10.1007/s00018-021-03770-5
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
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
Metabolic stress responses in mitochondrial diseases, ageing and cancer
Analysis of mitochondrial function using novel detection reagents
1DOJINDO LABORATORIES; 2Gunma University
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
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
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
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.
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
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
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
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
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
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
1. M. Puurand, M., Tepp, K., Timohhina, N., Aid, J., Shevchuk, I., Chekulayev, V., Kaambre, T. (2019). Tubulin betaII and betaIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease. Cells 8, doi:10.3390/cells8030239 (2019).
2. Makrecka-Kuka, M., Liepinsh, E., Murray, A.J., Lemieux, H., Dambrova, M., Tepp, K., Puurand, M., Kaambre, T., Han, W.H., de Goede, P., et al. (2019). Altered mitochondrial metabolism in the insulin-resistant heart. Acta Physiol (Oxf), e13430, doi:10.1111/apha.13430 (2019).
3. Tepp, K., M. Puurand, N. Timohhina, J. Aid-Vanakova, I. Reile, I. Shevchuk, V. Chekulayev, M. Eimre, N. Peet, L. Kadaja, K. Paju and T. Kaambre (2020). "Adaptation of striated muscles to Wolframin deficiency in mice: Alterations in cellular bioenergetics." Biochim Biophys Acta Gen Subj 1864(4): 129523.doi: 10.1016/j.bbagen.2020.129523
4. Koit, A., N. Timohhina, L. Truu, V. Chekulayev, S. Gudlawar, I. Shevchuk, K. Lepik, L. Mallo, R. Kutner, V. Valvere and T. Kaambre (2020). "Metabolic and OXPHOS Activities Quantified by Temporal ex vivo Analysis Display Patient-Specific Metabolic Vulnerabilities in Human Breast Cancers." Front Oncol 10: 1053.doi:10.3389/fonc.2020.01053
5. Rebane-Klemm, E., L. Truu, L. Reinsalu, M. Puurand, I. Shevchuk, V. Chekulayev, N. Timohhina, K. Tepp, J. Bogovskaja, V. Afanasjev, K. Suurmaa, V. Valvere and T. Kaambre (2020). "Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps." Cancers (Basel) 12(4). doi: 10.3390/cancers12040815
6. Klepinin, A., S. Zhang, L. Klepinina, E. Rebane-Klemm, A. Terzic, T. Kaambre and P. Dzeja (2020). "Adenylate Kinase and Metabolic Signaling in Cancer Cells." Front Oncol 10: 660.doi: 10.3389/fonc.2020.00660
7. Klepinina, L., Klepinin, A., Truu, L., Chekulayev, V., Vija, H., Kuus, K., Teino, I., Pook, M., Maimets, T., and Kaambre, T. *(2021). Colon cancer cell differentiation by sodium butyrate modulates metabolic plasticity of Caco-2 cells via alteration of phosphotransfer network. PLoS One 16, e0245348. doi: 10.1371/journal.pone.0245348
8. Reinsalu, L., Puurand, M., Chekulayev, V., Miller, S., Shevchuk, I., Tepp, K., Rebane-Klemm, E., Timohhina, N., Terasmaa, A., and Kaambre, T. *(2021). Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis. Frontiers in oncology 11, 698951. doi: 10.3389/fonc.2021.698951
9. Kaup, K.K., Toom, L., Truu, L., Miller, S., Puurand, M., Tepp, K., Kaambre, T., and Reile, I. (2021). A line-broadening free real-time (31)P pure shift NMR method for phosphometabolomic analysis. The Analyst 146, 5502-5507. doi: 10.1039/d1an01198g
10. Klepinin, A., Miller, S., Reile, I., Puurand, M., Rebane-Klemm, E., Klepinina, L., Vija, H., Zhang, S., Terzic, A., Dzeja, P., and Kaambre T*(2022). Stable Isotope Tracing Uncovers Reduced gamma/beta-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells. Frontiers in oncology 12, 892195. Doi: 10.3389/fonc.2022.892195
11. Tepp, K., Aid-Vanakova, J., Puurand, M., Timohhina, N., Reinsalu, L., Tein, K., Plaas, M., Shevchuk, I., Terasmaa, A., and Kaambre, T. (2022). Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles. Biochem Biophys Rep 30, 101250. Doi: 10.1016/j.bbrep.2022.101250
12. Gnaiger, E., Aasander, F., E, Abumrad, N., Acuna-Castroviejo, D., Adams, S., Ahn, B., Ali, S., Alves, M., Amati, F., Amoedo, N., et al. (2019). Mitochondrial respiratory states and rates. In MitoFit Preprint Arch (MitoFitPublication, MitoEAGLEPublication), pp. 40.
13. Mado, K., Chekulayev, V., Shevchuk, I., Puurand, M., Tepp, K., and Kaambre, T. (2019). On the role of tubulin, plectin, desmin, and vimentin in the regulation of mitochondrial energy fluxes in muscle cells. Am J Physiol Cell Physiol 316, C657-C667.
14. Rodriguez-Enriquez, S., Kaambre, T., and Moreno-Sanchez, R. (2020). Editorial: Metabolic Plasticity of Cancer. Frontiers in oncology 10, 599723.
15. Ruiz-Meana, M., Boengler, K., Garcia-Dorado, D., Hausenloy, D.J., Kaambre, T., Kararigas, G., Perrino, C., Schulz, R., and Ytrehus, K. (2020). Ageing, sex, and cardioprotection. Br J Pharmacol 177, 5270-5286.
16. Zhang, S., Yamada, S., Park, S., Klepinin, A., Kaambre, T., Terzic, A., and Dzeja, P. (2021). Adenylate kinase AK2 isoform integral in embryo and adult heart homeostasis. Biochem Biophys Res Commun 546, 59-64.
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)
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
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
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
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
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
1.Nouri, K. et al. Cell Death Dis 2020, 11, 841
2.Perrone, M.G. et al. Curr. Med. Chem. 2021, 28, 3287
3.Ishizawa, J. et al. Cancer Cell, 2019, 35, 721
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
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).
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
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.
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
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
[1] K. Čunátová, D.P. Reguera, M. Vrbacký, E. Fernández-Vizarra, S. Ding, I.M. Fearnley, M. Zeviani, J. Houštěk, T. Mráček, P. Pecina, Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis, Cells, 10 (2021).
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
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
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.
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
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
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
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
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
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
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.
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
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
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
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
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
1 He J, et al. Hum Brain Mapp. 2021
2 Manners DN, et al. Int J Environ Res Public Health. 2022
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
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.