Time: Monday, 12/June/2023: 6:00pm - 7:00pm |
Location: Bologna Congress Center Address: Piazza della Costituzione, 4/a, Bologna (BO), Italy |
- Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Maintenance on mitochondrial complexes ensures bioenergetic function in differentiated cells
1Institute for Cardiovascular Physiology, Goethe University Frankfurt, Germany; 2Molecular Bioinformatics, Goethe University, Frankfurt, Germany
[1] H. Heide, L. Bleier, M. Steger, J. Ackermann, S. Dröse, B. Schwamb, M. Zörnig, A.S. Reichert, I. Koch, I. Wittig, U.Brandt, Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex, Cell Metab. 16 (2012) 538–549.
[2] B. Schwanhäusser, M. Gossen, G. Dittmar, M. Selbach, Global analysis of cellular protein translation by pulsed SILAC, Proteomics 9 (2009) 205–209.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Investigating pathogenicity and tissue-specificity of mitochondrial aminoacyl-tRNA synthetase defects AARS2, EARS2 and RARS2 in neurons
Department of Clinical Neurosciences, University of Cambridge, United Kingdom
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mutations in Coq2 leads to severe developmental delay and early death in both zebrafish and mouse
1Ibs.Granada, Granada, Spain; 2Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 3Biofisika Institute (CSIC,UPV-EHU) and Department of Biochemistry and Molecular Biology, University of Basque Country, Leioa, Spain
1.Alcázar-Fabra, M., Rodríguez-Sánchez, F., Trevisson, E., & Brea-Calvo, G. (2021). Primary Coenzyme Q deficiencies: A literature review and online platform of clinical features to uncover genotype-phenotype correlations. Free Radical Biology and Medicine, 167, 141-180. https://doi.org/10.1016/j.freeradbiomed.2021.02.046
2.Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy. (2013). New England Journal of Medicine, 369(3), 233-244. https://doi.org/10.1056/nejmoa1212115
3.Jakobs, B. S., Van Den Heuvel, L. P., Smeets, R., De Vries, M., Hien, S., Schaible, T., Smeitink, J. A., Wevers, R. A., Wortmann, S. B., & Rodenburg, R. J. (2013). A novel mutation in COQ2 leading to fatal infantile multisystem disease. Journal of the Neurological Sciences, 326(1-2), 24-28. https://doi.org/10.1016/j.jns.2013.01.004
4.Herebian, D., Seibt, A., Smits, S. H. J., Rodenburg, R. J., & Mayatepek, E. (2017). 4-Hydroxybenzoic acid restores CoQ10biosynthesis in human COQ2 deficiency. Annals of clinical and translational neurology, 4(12), 902-908. https://doi.org/10.1002/acn3.486
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Pathogenic variants of the mitochondrial metallochaperone SCO1 result in a severe, combined COX and copper deficiency that causes a dilated cardiomyopathy in the murine heart.
1University of Saskatchewan, Canada; 2Auburn University
Glerum DM, Shtanko A, Tzagoloff A. Characterization of COX17, a yeast gene involved in copper metabolism and assembly of cytochrome oxidase. J Biol Chem. 1996 Jun 14;271(24):14504-9. doi: 10.1074/jbc.271.24.14504. PMID: 8662933.
Srinivasan C, Posewitz MC, George GN, Winge DR. Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae. Biochemistry. 1998 May 19;37(20):7572-7. doi: 10.1021/bi980418y. PMID: 9585572.
Hlynialuk CJ, Ling B, Baker ZN, Cobine PA, Yu LD, Boulet A, Wai T, Hossain A, El Zawily AM, McFie PJ, Stone SJ, Diaz F, Moraes CT, Viswanathan D, Petris MJ, Leary SC. The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis. Cell Rep. 2015 Feb 17;10(6):933-943. doi: 10.1016/j.celrep.2015.01.019. Epub 2015 Feb 13. PMID: 25683716.
Baker ZN, Jett K, Boulet A, et al. The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart. Hum Mol Genet. 2017;26(23):4617-4628. doi:10.1093/hmg/ddx344
Leary, S.C., Antonicka, H., Sasarman, F., Weraarpachai, W., Cobine, P.A., Pan, M., Brown, G.K., Brown, R., Majewski, J., Ha, K.C.H., et al. (2013a). Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic acidosis. Hum. Mutat. 34, 1366–1370.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Tissue-specific adaptation of stress responses upon COX10 deficiency
1CECAD Research Center, Germany; 2Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Using iPSC-derived neurons to unravel the pathomechanisms of Leber’s hereditary optic neuropathy
1Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 2IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy; 3Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy; 4National Research Council (CNR), Institute of Neuroscience, Milan, Italy; 5Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies, University of Ferrara, 44121 Ferrara, Italy; 6Maria Cecilia Hospital, GVM Care & Research, 48033, Cotignola, Ravenna, Italy; 7Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
Danese A, Patergnani S, Maresca A, Peron C, Raimondi A, Caporali L, Marchi S, La Morgia C, Del Dotto V, Zanna C, Iannielli A, Segnali A, Di Meo I, Cavaliere A, Lebiedzinska-Arciszewska M, Wieckowski MR, Martinuzzi A, Moraes-Filho MN, Salomao SR, Berezovsky A, Belfort R Jr, Buser C, Ross-Cisneros FN, Sadun AA, Tacchetti C, Broccoli V, Giorgi C, Tiranti V, Carelli V, Pinton P. Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy. Cell Rep. 2022 Jul 19;40(3):111124. doi: 10.1016/j.celrep.2022.111124. PMID: 35858578; PMCID: PMC9314546.
Peron C, Maresca A, Cavaliere A, Iannielli A, Broccoli V, Carelli V, Di Meo I, Tiranti V. Exploiting hiPSCs in Leber's Hereditary Optic Neuropathy (LHON): Present Achievements and Future Perspectives. Front Neurol. 2021 Jun 8;12:648916. doi: 10.3389/fneur.2021.648916. PMID: 34168607; PMCID: PMC8217617.
Peron C, Mauceri R, Cabassi T, Segnali A, Maresca A, Iannielli A, Rizzo A, Sciacca FL, Broccoli V, Carelli V, Tiranti V. Generation of a human iPSC line, FINCBi001-A, carrying a homoplasmic m.G3460A mutation in MT-ND1 associated with Leber's Hereditary optic Neuropathy (LHON). Stem Cell Res. 2020 Oct;48:101939. doi: 10.1016/j.scr.2020.101939. Epub 2020 Aug 3. PMID: 32771908.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Stem cell modelling of mitochondrial disease-linked cardiomyopathy
1Murdoch Children’s Research Institute, The Royal Children's Hospital, Melbourne, VIC, Australia; 2Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia; 3Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia; 4Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia; 5Victorian Clinical Genetics Services, The Royal Children’s Hospital, Melbourne, VIC, Australia; 6The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Melbourne, VIC, Australia; 7Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia; 8Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Melbourne, VIC, Australia
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Biochemical and computational approaches to dissect the effect of MT-CYB pathogenic mutations on respiratory chain activity and assembly
Department of Pharmacy and Biotechnology, University of Bologna, Italy
1 Fernández-Vizarra E, Ugalde C. Cooperative assembly of the mitochondrial respiratory chain. Trends Biochem Sci. 2022
2 Rugolo M, Zanna C, Ghelli AM. Organization of the Respiratory Supercomplexes in Cells with Defective Complex III: Structural Features and Metabolic Consequences. Life (Basel). 2021
3 Mishra SK. PSP-GNM: Predicting Protein Stability Changes upon Point Mutations with a Gaussian Network Model. Int J Mol Sci. 2022
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Exploring the assembly and maintenance of mitochondrial complex I by complexome profiling-based approaches
1Institute for Cardiovascular Physiology, Goethe University Frankfurt, Germany; 2Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands
[1] S. Guerrero-Castillo, F. Baertling, D. Kownatzki, H.J. Wessels, S. Arnold, U. Brandt, L. Nijtmans, The Assembly Pathway of Mitochondrial Respiratory Chain Complex I, Cell metabolism, 25 (2017) 128-139.
[2] H. Heide, L. Bleier, M. Steger, J. Ackermann, S. Drose, B. Schwamb, M. Zornig, A.S. Reichert, I. Koch, I. Wittig, U. Brandt, Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex, Cell metabolism, 16 (2012) 538-549.
[3] A. Cabrera-Orefice, A. Potter, F. Evers, J.F. Hevler, S. Guerrero-Castillo, Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease, Front Cell Dev Biol, 9 (2022) 796128.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Functional involvement of actin-binding Gelsolin on mitochondrial Oxphos dysfunction
Fundación Hospital 12 de Octubre, Spain
García-Bartolomé, A., Peñas, A., Illescas, M., Bermejo, V., López-Calcerrada, S., Pérez-Pérez, R., et al. (2020). Altered Expression Ratio of Actin-Binding Gelsolin Isoforms Is a Novel Hallmark of Mitochondrial OXPHOS
Dysfunction. Cells 9, 1922–21. doi:10.3390/cells9091922
Peñas, A., Fernández-De la Torre, M., Laine-Menéndez, S., Lora, D., Illescas, M., García-Bartolomé, A., et al. (2021). Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders. Ijms 22, 6396. doi:10.3390/ijms22126396
Illescas M, Peñas A, Arenas J, Martín MA and Ugalde C. 2021. Regulation of Mitochondrial Function by the Actin Cytoskeleton. Front. Cell Dev. Biol. 9:795838. doi: 10.3389/fcell.2021.795838.
Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C. 2022 Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. doi: 10.1016/j.cmet.2022.09.005
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
In vivo role of respiratory complex I NDUFA10 subunit in dNTP homeostasis
1Research Group on Neuromuscular and Mitochondrial Disorders, Vall d’Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; 2Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; 3BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), University of Barcelona, Barcelona 08028, Spain. and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain.; 4Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia; 5Instituto de Investigación, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041 Madrid, Spain.; 6Laboratory of Metabolism and Obesity, Vall d'Hebron - Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERDEM, CIBER on Diabetes and Associated Metabolic Diseases, Instituto de Salud Carlos III, Barcelona, Spain
Molina-Granada D, González-Vioque E, Dibley MG, Cabrera-Pérez R, Vallbona-Garcia A, Torres-Torronteras J, Sazanov LA, Ryan MT, Cámara Y, Martí R. Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit. Commun Biol. 2022 Jun 23;5(1):620. doi: 10.1038/s42003-022-03568-6. PMID: 35739187; PMCID: PMC9226000.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Modeling POLRMT pathogenic variants in the mouse
1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden; 3Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
The role of the CCR4 family member ANGEL1 in the expression of mitochondrial-targeted proteins
1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; 2Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden
Chang, K§., Liu, P§., Requejo, G & Bai, H. (2022). mTORC2 protects the heart from high-fat diet-induced cardiomyopathy through mitochondrial fission in Drosophila. Front. Cell Dev. Biol., 2022. https://doi.org/10.3389/fcell.2022.866210
§These authors contributed equally to this work
Birnbaum, A., Chang, K., & Bai, H. (2020). FOXO regulates neuromuscular junction homeostasis during Drosophila aging. Front Aging Neurosci, 2021 Jan 27; 12:567861. DOI: 10.3389/fnagi.2020.567861.
Huang, K., Miao, T., Chang, K. et al. Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine. Nat Commun 11, 2943 (2020). https://doi.org/10.1038/s41467-020-16781-w
Kai Chang§, Ping Kang§, Ying Liu, Kerui Huang, Ting Miao, Antonia P. Sagona, Ioannis P. Nezis, Rolf Bodmer, Karen Ocorr & Hua Bai (2019) TGFB-INHB/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2, Autophagy, DOI: 10.1080/15548627.2019.1704117
§These authors contributed equally to this work
Kang, P., Chang, K., Liu, Y. et al. Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO. Sci Rep 7, 16369 (2017) doi:10.1038/s41598-017-16638-1
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Tissue-specific bioenergetics in mouse models of mitochondrial disease
1Università di Padova; 2Semmelweis University; 3Universität Innsbruck; 4University of Sussex
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Yeast as a tool to investigate variants in mtARS genes associated with mitochondrial diseases
1Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; 2Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 3Department of Medical Physiopathology and Transplantation, University of Milan, Milan, Italy
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
A mutation in mouse mt-Atp6 gene induces respiration defects and opposed effects on the cell tumorigenic phenotype
1University of Zaragoza, Spain; 2University of Zaragoza, Peaches Biotech Group, Spain; 3Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Spain
1.Moreno-Loshuertos, R.; Marco-Brualla, J.; Meade, P.; Soler-Agesta, R.; Enriquez, J. A.; Fernandez-Silva, P., How hot can mitochondria be? Incubation at temperatures above 43 degrees C induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria. Mitochondrion 2023, 69, 83-94.
2.Moreno-Loshuertos, R.; Movilla, N.; Marco-Brualla, J.; Soler-Agesta, R.; Ferreira, P.; Enriquez, J. A.; Fernandez-Silva, P., A Mutation in Mouse MT-ATP6 Gene Induces Respiration Defects and Opposed Effects on the Cell Tumorigenic Phenotype. Int J Mol Sci 2023, 24, (2).
3.Novo, N.; Romero-Tamayo, S.; Marcuello, C.; Boneta, S.; Blasco-Machin, I.; Velázquez-Campoy, A.; Villanueva, R.; Moreno-Loshuertos, R.; Lostao, A.; Medina, M.; Ferreira, P., Beyond a platform protein for the degradosome assembly: The Apoptosis-Inducing Factor as an efficient nuclease involved in chromatinolysis. PNAS Nexus 2022, 2, (2).
4.Soler-Agesta, R.; Marco-Brualla, J.; Minjarez-Saenz, M.; Yim, C. Y.; Martinez-Julvez, M.; Price, M. R.; Moreno-Loshuertos, R.; Ames, T. D.; Jimeno, J.; Anel, A., PT-112 Induces Mitochondrial Stress and Immunogenic Cell Death, Targeting Tumor Cells with Mitochondrial Deficiencies. Cancers (Basel) 2022, 14, (16).
5.Pinol, R.; Zeler, J.; Brites, C. D. S.; Gu, Y.; Tellez, P.; Carneiro Neto, A. N.; da Silva, T. E.; Moreno-Loshuertos, R.; Fernandez-Silva, P.; Gallego, A. I.; Martinez-Lostao, L.; Martinez, A.; Carlos, L. D.; Millan, A., Real-Time Intracellular Temperature Imaging Using Lanthanide-Bearing Polymeric Micelles. Nano Lett 2020, 20, (9), 6466-6472.
6.Gu, Y.; Yoshikiyo, M.; Namai, A.; Bonvin, D.; Martinez, A.; Pinol, R.; Tellez, P.; Silva, N. J. O.; Ahrentorp, F.; Johansson, C.; Marco-Brualla, J.; Moreno-Loshuertos, R.; Fernandez-Silva, P.; Cui, Y.; Ohkoshi, S. I.; Millan, A., Magnetic hyperthermia with epsilon-Fe(2)O(3) nanoparticles. RSC Adv 2020, 10, (48), 28786-28797.
7.Delavallee, L.; Mathiah, N.; Cabon, L.; Mazeraud, A.; Brunelle-Navas, M. N.; Lerner, L. K.; Tannoury, M.; Prola, A.; Moreno-Loshuertos, R.; Baritaud, M.; Vela, L.; Garbin, K.; Garnier, D.; Lemaire, C.; Langa-Vives, F.; Cohen-Salmon, M.; Fernandez-Silva, P.; Chretien, F.; Migeotte, I.; Susin, S. A., Mitochondrial AIF loss causes metabolic reprogramming, caspase-independent cell death blockade, embryonic lethality, and perinatal hydrocephalus. Mol Metab 2020, 40, 101027.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
A systemic Muscle-WAT crosstalk progressively depletes protein and fat stores aggravating mitochondrial myopathy.
1Weill Cornell Medicine, Brain and Mind Research Institute, New York, NY; 2Weill Cornell Medicine, Department of Pharmacology, New York, NY; 3Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
A novel mitochondrial assembly factor RTN4IP1 has an essential role in the final stages of Complex I assembly
1Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 2Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne, UK; 3Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; 4Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA; 5Functional Proteomics Group, Institute for Cardiovascular Physiology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany
1 Charif M et al. Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults. JAMA Neurol. 2017
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
ETFDH supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis
1Department of Molecular Biology, Centro de Biología Molecular "Severo Ochoa" (CBMSO-UAM-CSIC), Madrid, Spain; 2Instituto Universitario de Biología Molecular (IUBM), Autonomous University of Madrid, Madrid, Spain; 3Centro de Investigación Biomédica en red de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain; 4Instituto de Investigación Hospital 12 de octubre, i+12, Universidad Autónoma de Madrid, Madrid, Spain
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Metabolic rewiring as an adaptive mechanism in COX null cells
1Department of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 2Faculty of Science, Charles University, 12800 Prague, Czech Republic; 3Laboratory of Translational Metabolomics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Metabolic rewiring due to progressive increase in mtDNA mutation heteroplasmy reveals markers of disease severity
1North-West University, South Africa; 2Osaka University, Japan; 3Radboud University Medical Center, Netherlands; 4University of Tsukuba, Japan
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Novel or rare AIFM1 pathogenic variants: their impact on mitochondrial metabolism and clinical manifestation in eight patients, including 3 girls
1Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague; 2Institute of Molecular and Clinical Pathology and Medical Genetics, University Hospital Ostrava
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Pathological molecular mechanisms underlying COA8 loss of function
1Department of Biomedical Sciences, University of Padova, Padova, Italy; 2Veneto Institute of Molecular Medicine, Padova, Italy; 3Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; 4University of Texas Southwestern Medical Center, Dallas, TX, USA; 5Department of Chemical Sciences, University of Padova, Padova, Italy; 6Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; 7Department of Neurosciences, University of Padova, Padova, Italy
Hedberg-Oldfors, C., Darin, N., Thomsen, C., Lindberg, C., and Oldfors, A. (2020). COX deficiency and leukoencephalopathy due to a novel homozygous APOPT1/COA8 mutation. Neurol Genet 6, e464.
Melchionda, L., Haack, T.B., Hardy, S., Abbink, T.E., Fernandez-Vizarra, E., Lamantea, E., Marchet, S., Morandi, L., Moggio, M., Carrozzo, R., et al. (2014). Mutations in APOPT1, Encoding a Mitochondrial Protein, Cause Cavitating Leukoencephalopathy with Cytochrome c Oxidase Deficiency. Am J Hum Genet 95, 315-325.
Pei, J., Zhang, J., and Cong, Q. (2022). Human mitochondrial protein complexes revealed by large-scale coevolution analysis and deep learning-based structure modeling. Bioinformatics.
Sharma, S., Singh, P., Fernandez-Vizarra, E., Zeviani, M., Van der Knaap, M.S., and Saran, R.K. (2018). Cavitating Leukoencephalopathy With Posterior Predominance Caused by a Deletion in the APOPT1 Gene in an Indian Boy. J Child Neurol 33, 428-431.
Signes, A., Cerutti, R., Dickson, A.S., Beninca, C., Hinchy, E.C., Ghezzi, D., Carrozzo, R., Bertini, E., Murphy, M.P., Nathan, J.A., et al. (2019). APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS. EMBO molecular medicine 11.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Retinal pathophysiology characterisation of the novel mitochondrial heteroplasmy mouse model
1University of Cambridge, United Kingdom; 2Newcastle University, United Kingdom
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Impaired spermatogenesis driven by mitochondrial dysfunction and ferroptosis in primary spermatocytes in a mouse model of Leigh syndrome
1University of Pennsylvania,USA; 2University of Angers, SFR ICAT, SCIAM, 49000 Angers, France; 3MITOLAB, University of Angers, INSERM U1083, France; 4Pablo de Olavide University, Spain; 5Neuromuscular Reference Center CHU Angers, France
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mitophagy dysfunction in mitochondrial myopathy and therapy by mitophagy activator CAP1902
1STEMM Research Program, Biomedicum Helsinki, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 2Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 3Department of Pharmacology, Center for Innovations in Brain Science, University of Arizona, Tucson, AZ, USA; 4Department of Medicine, Endocrinology, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mtfp1 controls oxidative phosphorylation and cell death in liver disease
1Institut Pasteur, Mitochondrial Biology Group, CNRS UMR 3691, Université Paris Cité, Paris, France.; 2Institut Pasteur, Biomics Technological Platform, Université Paris Cité, Paris, France.; 3Institut Pasteur, Bioinformatics and Biostatistics Hub, Université Paris Cité, Paris, France.; 4Institut Pasteur, Proteomics Core Facility, MSBio UtechS, UAR CNRS 2024, Université Paris Cité, Paris, France.; 5Institut Pasteur Ultrastructural Bio Imaging, UTechS, Université Paris Cité, Paris, France.; 6Platform for Metabolic Analyses, SFR Necker, INSERM US24/CNRS UMS 3633, Paris, France.; 7Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Non-canonical function of succinate dehydrogenase assembly factor 2 (SDHAF2) during OXPHOS dysfunction
1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia; 2Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; 3Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia; 4Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia; 5Victorian Clinical Genetics Services, Royal Children's Hospital, Parkville, VIC, Australia
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
NUAK1-dependent metabolic underpinnings of adult muscle stem cells
Physiopathology and Genetics of Neurons and Muscles Laboratory, Institut NeuroMyoGène, Lyon, France
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
A novel approach to measure complex V ATP hydrolysis in frozen cell lysates and tissue homogenates
1Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095 USA; 2Metabolism Theme, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA; 3Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA; 4Molecular & Cellular Integrative Physiology, University of California, Los Angeles, CA, 90095, USA.; 5Institut de Biologia Molecular de Barcelona, IBMB-CSIC, Barcelona, Catalonia, 08028, Spain
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
OxPhos defects cause cell-autonomous and whole-body signs of hypermetabolism in cells and in patients with mitochondrial diseases
1Columbia University Irving Medical Center, United States of America; 2University of Florida, United States of America; 3Angers University, UMR CNRS 6015 - INSERM U1083, MitoVasc Institute, Angers, France; 4Yale University, United States of America; 5University of Pennsylvania, United States of America; 6Stanford University, United States of America; 7University of California San Francisco, United States of America; 8Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 9University of Copenhagen, Denmark; 10University of Udine, Italy; 11Altos labs, United States of America; 12University of Texas Southwestern Medical Center, United States of America; 13University of Pittsburgh, United States of America; 14Thomas Jefferson University, United States of America
Sturm G et al. A multi-omics longitudinal aging dataset in primary human fibroblasts with mitochondrial perturbations. Sci Data 9, 751 (2022). https://doi.org/10.1038/s41597-022-01852-y
Sturm G. et al. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Commun Biol 6, 22 (2023). https://doi.org/10.1038/s42003-022-04303-x
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Dysfunction of mitochondrial chaperone HSP60 triggers disruption of mitochondrial pathways activating multiple regulatory responses
1Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 2Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark; 3Department of Forensic Medicine, Aarhus University, Aarhus, Denmark; 4Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
1. Bie AS, Cömert C, Körner R, et al. An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. Cell Stress Chaperones. 2020;25(3):407-416.
2. Bross P, Naundrup S, Hansen J, et al. The Hsp60-(p.V98I) mutation associated with hereditary spastic paraplegia SPG13 compromises chaperonin function both in vitro and in vivo. J Biol Chem. 2008;283(23):15694-15700.
3. Magen D, Georgopoulos C, Bross P, et al. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet. 2008;83(1):30-42.
4. Cömert C, Brick L, Ang D, et al. A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy. Cold Spring Harb Mol Case Stud. 2020;6(3):a004879. Published 2020 Jun 12.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Generation of iPSCs derived neural progenitors and cardiomyocytes as cellular models to study the pathophysiology of Pearson Syndrome
1Unit of Medical genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; 2Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy; 3Department of Biotechnology and Biosciences, University of Milano - Bicocca, Milan, Italy
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
High aerobic exercise capacity predicts increased mitochondrial response to exercise training
1Department of Cardiothoracic Surgery, University Hospital of Friedrich-Schiller-University Jena, Germany; 2Department of Physiology and Pharmacology, University of Toledo, Toledo, OH, United States; 3Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States
Heyne E, Schrepper A, Doenst T, Schenkl C, Kreuzer K, Schwarzer M. High-fat diet affects skeletal muscle mitochondria comparable to pressure overload-induced heart failure. J Cell Mol Med. 2020 Jun;24(12):6741-6749. doi: 10.1111/jcmm.15325. Epub 2020 May 4. PMID: 32363733; PMCID: PMC7299710.
Schwarzer M, Molis A, Schenkl C, Schrepper A, Britton SL, Koch LG, Doenst T. Genetically determined exercise capacity affects systemic glucose response to insulin in rats. Physiol Genomics. 2021 Sep 1;53(9):395-405. doi: 10.1152/physiolgenomics.00014.2021. Epub 2021 Jul 23. PMID: 34297615; PMCID: PMC8530732.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Investigating the role of LONP1 in heart and skeletal muscle metabolism
1Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), 50931 Cologne, Germany; 2Department III of Internal Medicine, Heart Center, University Hospital of Cologne, 50931 Cologne, Germany; 3Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mitochondrial dysfunction promotes liver fibrosis through the ACOT2-MCT6-OXCT1 axis.
1Karolinska Institutet, Sweden; 2Zhengzhou University, China; 3Norwegian Veterinary Institute, Norway
Zhou X, Mikaeloff F, Curbo S, Zhao Q, Kuiper R, Végvári Á, Neogi U, Karlsson A.Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.Hum Mol Genet. 2021 Oct 13;30(21):2012-2026
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
PNC2 (SLC25A36) deficiency associated with the hyperinsulinism/hyperammonemia syndrome
1Università degli Studi di Bari Aldo Moro, Italy; 2Libera Università Mediterranea Giuseppe Degennaro, Italy; 3Department of Pediatrics and Genetics, Al Makassed Hospital and Al-Quds University, Palestine.; 4Department of Genetics, Hadassah, Hebrew University Medical Center, Israel
[1] M.A. Shahroor, F.M. Lasorsa, V. Porcelli V, I. Dweikat, M.A. Di Noia, M. Gur, G. Agostino, A . Shaag A, T. Rinaldi, G. Gasparre, F. Guerra, A. Castegna, S. Todisco, B. Abu-Libdeh, O. Elpeleg, L. Palmieri, PNC2 (SLC25A36) Deficiency Associated With the Hyperinsulinism/Hyperammonemia Syndrome, J Clin Endocrinol Metab, 107(2022):1346-1356.
[2] L. Jasper, P. Scarcia, S. Rust, J. Reunert, F. Palmieri, T. Marquardt, Uridine Treatment of the First Known Case of SLC25A36 Deficiency, Int J Mol Sci. 22(2021) 9929.
[3] Safran A, Proskorovski-Ohayon R, Eskin-Schwartz M, Yogev Y, Drabkin M, Eremenko E, Aharoni S, Freund O, Jean MM, Agam N, Hadar N, Loewenthal N, Staretz-Chacham O, Birk OS.Hyperinsulinism/hyperammonemia syndrome caused by biallelic SLC25A36 mutation. J Inherit Metab Dis. 2023 Jan 25. doi: 10.1002/jimd.12594. Online ahead of print
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Cultured neurons with CoQ10 deficiency reveal alterations of lipid metabolism
1Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10032, United States; 2IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 3Institute of Biotechnology, Biomedical Research Center (CIBM), Health Science Technological Park (PTS), University of Granada, Armilla, Granada, 18100, Spain; 4Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, 986145 Nebraska Medical Center, Omaha, NE; 5Unita` di Genetica delle Malattie Neurodegenerative e Metaboliche, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, 20126, Italy
1. Turunen, M.; Olsson, J.; Dallner, G. Metabolism and function of coenzyme Q. Biochim. Biophys. Acta - Biomembr. 2004, 1660, 171–199, doi:10.1016/j.bbamem.2003.11.012.
2. Quinzii, C.M.; López, L.C.; Gilkerson, R.W.; Dorado, B.; Coku, J.; Naini, A.B.; Lagier-Tourenne, C.; Schuelke, M.; Salviati, L.; Carrozzo, R.; et al. Reactive oxygen species, oxidative stress, and cell death correlate with level of CoQ10 deficiency. FASEB J. 2010, 24, 3733–3743, doi:10.1096/fj.09-152728.
3. Emma, F.; Montini, G.; Parikh, S.M.; Salviati, L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. 2016, doi:10.1038/nrneph.2015.214.
4. Ernster, L.; Dallner, G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim. Biophys. Acta 1995, 1271, 195–204.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration
1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland; 2Biocenter Oulu, University of Oulu, Oulu, Finland; 3Faculty of Physics, University of Warsaw, Warsaw, Poland; 4Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany; 5Department of Biochemistry and Molecular Biology, University of Würzburg, Würzburg, Germany; 6Zentrum für Molekulare Biologie (ZMBH), DKFZ-ZMBH Alliance and Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany
Rahman M.T., Koski M.K., Panecka-Hofman J., Schmitz W, Kastaniotis A.J., Wade R.C., Wierenga R.K., Hiltunen J.K. & Autio K.J. (2023) An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration. Nature Communications 14(1):619. doi: 10.1038/s41467-023-36358-7
Alam J., Sah-Teli S.K., Venkatesan R., Koski M.K., Autio K.J., Hiltunen J K. & Kastaniotis A.J. (2021) Biophysical and structural analysis of the SAM-dependent Saccharomyces cerevisiae methyltransferase family protein Rsm22. Acta Crystallographica Section D. 77:840-853
Kastaniotis A.J., Autio K.J. & Nair R.R. (2021) Mitochondrial fatty acids and neurodegenerative disorders. Neuroscientist 27(2):143-158
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Antibiotics directly affect mitochondrial respiration
1Technische Universität München, Germany; 2Oroboros Instruments GmbH, Innsbruck, Austria; 3Helmholtz Zentrum München, Germany
[1] Tarantino G. et al. (2017): Hepatol Res. 37:410‐415
[2] O'Reilly M. et al. (2019):. Front Cell Neurosci. 13;13:416. doi: 10.3389/fncel.2019.00416.
[3] Oyebode OT. et al. (2018) Toxicology Mechanisms and Methods, 1–31.doi:10.1080/15376516.2018.1528651
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Can transmission of mitochondria over the species barrier promote climate change adaptation?
1Tampere University, Finland; 2University of Eastern Finland
Gaertner K, Michell C, Tapanainen R, et al. Molecular phenotyping uncovers differences in basic housekeeping functions among closely related species of hares (Lepus spp., Lagomorpha: Leporidae) [published online ahead of print, 2022 Nov 1]. Mol Ecol. 2022; doi:10.1111/mec.16755
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Developing an in vitro model to study the impact of the m.3243A>G mutation in iPSC-derived myofibers
University College London, United Kingdom
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Discordant phenotype in fibroblast cell lines generated from the same MELAS patient
1IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; 2Department of Biomedical and Neuromuscular Sciences (DIBINEM), University of Bologna
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Generation of a novel CoQ deficient mouse model to elucidate the role of COQ4
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
1.Guerra, R.M. and D.J. Pagliarini, Coenzyme Q biochemistry and biosynthesis. Trends Biochem Sci, 2023.
2.Alcázar-Fabra, M., E. Trevisson, and G. Brea-Calvo, Clinical syndromes associated with Coenzyme Q. Essays Biochem, 2018. 62(3): p. 377-398.
3.Belogrudov, G.I., et al., Yeast COQ4 encodes a mitochondrial protein required for coenzyme Q synthesis. Arch Biochem Biophys, 2001. 392(1): p. 48-58.
4.Casarin, A., et al., Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis. Biochem Biophys Res Commun, 2008. 372(1): p. 35-9.
5.Marbois, B., et al., Coq3 and Coq4 define a polypeptide complex in yeast mitochondria for the biosynthesis of coenzyme Q. J Biol Chem, 2005. 280(21): p. 20231-8.
6.Marbois, B., et al., The yeast Coq4 polypeptide organizes a mitochondrial protein complex essential for coenzyme Q biosynthesis. Biochim Biophys Acta, 2009. 1791(1): p. 69-75.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Perivascular adipose tissue remodeling impairs mitochondrial function in thermoneutral-housed rats
1University of Colorado/Rocky Mountain Regional VA Medical Center, United States of America; 2Cornell College, United States of America
1. Chun J.H., Henckel M.M., Knaub L.A., Hull S.E., Pott G.B., Ramirez D.G., Reusch J.E.-B., Keller A.C. (-)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality. Planta Med. 2022 Aug;88(9-10):735-744. doi: 10.1055/a-1843-9855.
2. Keller A.C., Chun J.H., Knaub L.A., Henckel M.M., Hull S.E., Scalzo R.L., Pott G.B., Walker L.A., Reusch J.E.-B. Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease. J Hypertens. 2022 Nov 1;40(11):2133-2146. doi: 10.1097/HJH.0000000000003153.
3. Vaughan O.R., Rosario F.J., Chan J., Cox L.A., Ferchaud-Roucher V., Zemski-Berry K.A., Reusch J.E.- B., Keller A.C., Powell T.L., Jansson T. Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice. J Physiol. 2022 Jul;600(13):3169-3191. doi: 10.1113/JP282462.
4. Chun J.H., Henckel M.M., Knaub L.A., Hull S.E., Pott G., Walker, L.A., Reusch J.E.B., Keller A.C. (–)-Epicatechin improves vasoreactivity and mitochondrial respiration in thermoneutral-housed Wistar rat vasculature. Nutrients. 2022 14(5), 1097;doi.org/10.3390/nu14051097.
5. Keller, A.C., Hull, S.E., Elajaili, H., Johnston, A., Knaub, L.A., Chun, J.H., Walker, L.A., Nozik-Grayck, E., Reusch, J.E.-B. (–)-Epicatechin Modulates Mitochondrial Redox in Vascular Cell Models of Oxidative Stress. Oxidative Medicine and Cellular Longevity. 2020. doi.org/10.1155/2020/6392629
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Temporal analysis of mitochondrial complexome profiling coupled to multi-omics analysis unveils implications of CIV remodelling in postnatal heart development
University of Cologne, Germany
1. Porter Jr G., et al. (2011) Bioenergetics, mitochondria, and cardiac myocyte differentiation. Prog. Pediatr. Cardiol. 31, 75–81. doi: 10.1016/j.ppedcard.2011.02.002;
2. Gan J., Sonntag H-J., Tang Mk., Cai D., Lee KKH. (2015) Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome. PLoS ONE 10 (7): e0133288. doi:10.1371/journal.pone.0133288
3. Gu Y., et al. (2022) Multi-omics profiling visualizes dynamics of cardiac development and functions, Cell Reports, Volume 41, Issue 13,111891, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2022.111891.
4.Talman V., et al. (2018). Molecular Atlas of Postnatal Mouse Heart Development. J Am Heart Assoc. 2018;7:e010378. DOI: 10.1161/JAHA.118.010378
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mitochondrial dysfunction in immune cells leads to distinct transcriptome profile and improved immune competence in Drosophila
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Molecular Biology, Umeå University, Umeå, Sweden; 3Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, United Kingdom
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Molecular mechanisms of extraocular muscle manifestation in mitochondrial myopathy
STEMM, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
Forsström, S., Jackson, C. B., Carroll, C. J., Kuronen, M., Pirinen, E., Pradhan, S., … Suomalainen, A. (2019). Fibroblast Growth Factor 21 Drives Dynamics of Local and Systemic Stress Responses in Mitochondrial Myopathy with mtDNA
Deletions. Cell Metabolism, 1–15. https://doi.org/10.1016/j.cmet.2019.08.019.
Khan, N. A., Nikkanen, J., Yatsuga, S., Jackson, C., Wang, L., Pradhan, S., … Suomalainen, A. (2017). mTORC1 Regulates
Mitochondrial Integrated Stress Response and Mitochondrial Myopathy Progression. Cell Metabolism, 26(2), 419-428.e5.
https://doi.org/10.1016/j.cmet.2017.07.007
Pradhan, S...Lopus M (2017) “Elucidation of the Tubulin-Targeted Mechanism of Action of 9-(3-Pyridyl) Noscapine.” Cur.
Top. in Medicinal Chemistry, vol. 17, no. 22, 2017, pp. 2569–74, doi:http://dx.doi.org/10.2174/1568026617666170104150304.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Redox metabolites and transporters: Differential expression and ratios in specific Ndufs4 knockout mice organs.
Human Metabolomics, North-West University, South Africa
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
What makes folding of a mitochondrial protein dependent on the HSP60/HSP10 chaperone complex?
Aarhus University and Aarhus University Hospital, Denmark
1.Henriques, B. J., Katrine Jentoft Olsen, R., Gomes, C. M., andBross, P. (2021) Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease Gene 145407 10.1016/j.gene.2021.145407
2.Cömert, C., Brick, L., Ang, D., Palmfeldt, J., Meaney, B. F., Kozenko, M. et al. (2020) A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy Cold Spring Harb Mol Case Stud 6, 10.1101/mcs.a004879
3.Bie, A. S., Comert, C., Korner, R., Corydon, T. J., Palmfeldt, J., Hipp, M. S. et al. (2020) An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space Cell Stress Chaperones 25, 407-416 10.1007/s12192-020-01080-6
4.Palmfeldt, J., andBross, P. (2017) Proteomics of human mitochondria Mitochondrion 33, 2-14 10.1016/j.mito.2016.07.006
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
OXPHOS composition is altered in the FXNI151F mouse model of Friedreich Ataxia in a progressive and a tissue-specific way
Dept. Ciències Mèdiques Bàsiques, Fac. Medicina, Universitat de Lleida. IRB Lleida.
Medina-Carbonero M, Sanz-Alcázar A, Britti E, Delaspre F, Cabiscol E, Ros J, Tamarit J. Mice harboring the FXN I151F pathological point mutation present decreased frataxin levels, a Friedreich ataxia-like phenotype, and mitochondrial alterations. Cell Mol Life Sci. 2022 Jan 17;79(2):74.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Disease causing-Mfn2 mutations alter mitochondrial fusion and fission dynamics and metabolism.
1Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK.; 2School of Biological Sciences, Department of Cellular and Molecular Biology, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Dissecting the mitochondrial disease-associated ATAD3 gene cluster and its pathogenic variants
1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria,Australia; 2Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia; 3Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; 4Ian Holmes Imaging Centre, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia; 5Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Victoria, Australia; 6Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia; 7Harry Perkins Institute of Medical Research and The University of Western Australia Centre for Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia; 8ARC Centre of Excellence in Synthetic Biology, QEII Medical Centre and University of Western Australia, Nedlands, Western Australia, Australia; 9Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, Australia; 10Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Dynamics of adenine nucleotides in colorectal cancer clinical material
1National Institute of Chemical Physics and Biophysics, Estonia; 2Tallinn University of Technology, Estonia; 3North Estonia Medical Centre
Klepinin, A., Miller, S., Reile, I., Puurand, M., Rebane-Klemm, E., Klepinina, L., Vija, H., Zhang, S., Terzic, A., Dzeja, P., & Kaambre, T. (2022). Stable Isotope Tracing Uncovers Reduced γ/β-ATP Turnover and Metabolic Flux Through Mitochondrial-Linked Phosphotransfer Circuits in Aggressive Breast Cancer Cells. Frontiers in oncology, 12, 892195. https://doi.org/10.3389/fonc.2022.892195
Reinsalu, L., Puurand, M., Chekulayev, V., Miller, S., Shevchuk, I., Tepp, K., Rebane-Klemm, E., Timohhina, N., Terasmaa, A., & Kaambre, T. (2021). Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis. Frontiers in oncology, 11, 698951. https://doi.org/10.3389/fonc.2021.698951
Kaup, K. K., Toom, L., Truu, L., Miller, S., Puurand, M., Tepp, K., Käämbre, T., & Reile, I. (2021). A line-broadening free real-time 31P pure shift NMR method for phosphometabolomic analysis. The Analyst, 146(18), 5502–5507. https://doi.org/10.1039/d1an01198g
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
The role of SURF1 protein in cytochrome c oxidase biogenesis
1Institute of Physiology of the Czech Academy of Sciences, Czech Republic; 2Institute of Microbiology, Czech Academy of Sciences, Trebon, Czech Republic; 3Departement of Biomedical Sciences, University of Padova, Padova, Italy; 4Departement of Neurosciences, University of Padova, Padova, Italy
N. Kovářová, P. Pecina, H. Nůsková, M. Vrbacký, M. Zeviani, T. Mráček, C. Viscomi, J. Houštěk, Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects, BBA, 1862 (2016), 705-15.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Depicting inclusion body myositis using a patient-derived fibroblast model
1Laboratory of Inherited Metabolic Disorders and Muscle Disease, Centre de Recerca Biomèdica CELLEX - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; 2Department of Internal Medicine, Hospital Clinic of Barcelona, Barcelona, Spain; 3CIBERER— Spanish Biomedical Research Centre in Rare Diseases, Madrid, Spain; 4CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain; 5Universitat Pompeu Fabra (UPF), Barcelona, Spain; 6Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu; Esplugues de Llobregat, Barcelona, Spain; 7Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB-CSIC), Liver Unit-HCB-IDIBAPS, Barcelona, Spain; 8CIBEREHD-Spanish Biomedical Research Centre in Hepatic and Digestive Diseases, Madrid, Spain; 9Department of Biomedicine, Cell Biology Unit, CELLEX-IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Effect of physiological cell culture media on cell viability and NRF2 activation
National Institute of Chemical and Biological Physics, Estonia
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Genetic and functional characterization of a new patient with COX4I1 deficiency
1Hospital Clinic, IDIBAPS, CIBERER, Barcelona, Spain; 2Hospital Universitario de Cruces, Spain
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Application of the Escherichia coli Model System to Study the Human Polyribonucleotide Phosphorylase
Università degli Studi di Milano, Italy
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Phase two biotransformation is highly affected by mitochondrial disease: considerations for pharmacological therapies.
Human Metabolomics, North-West University, South Africa
1.Kühn, S., Williams, M. E., Dercksen, M., Sass, J. O., & van der Sluis, R. (2023). The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA-an in-silico and in vitro validation. Computational and Structural Biotechnology Journal, 21, 1236-1248. https://doi.org/10.1016/j.csbj.2023.01.041
2.Gruosso, F., Montano, V., Simoncini, C., Siciliano, G., & Mancuso, M. (2020). Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020. Journal of Clinical Medicine, 10(1), 94. MDPI AG. Retrieved from http://dx.doi.org/10.3390/jcm10010094
3.Fouché, B. R. (2021). Differential expression of genes involved in phase two biotransformation in an NDUFS4 deficient mouse model (Master’s dissertation, North-West University (South Africa)). http://hdl.handle.net/10394/38596
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mitochondrial phenotyping of fibroblasts from Kearns Sayre’s patients to model the disease
1Laboratory of Inherited Metabolic Disorders and Muscle Disease, Centre de Recerca Biomèdica CELLEX - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Sciences - Universitat de Barcelona (UB); Barcelona, Spain.; 2Internal Medicine Department - Hospital Clínic de Barcelona; Barcelona, Spain.; 3CIBERER—Spanish Biomedical Research Centre in Rare Diseases; Madrid, Spain.; 4Hospital Sant Joan de Déu (HSJdD) de Barcelona, Barcelona, Spain.; 5Grupo de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (imas12). Madrid. Spain.; 6Centro de Biología Molecular S.O., Universidad Autónoma de Madrid (UAM); Madrid, Spain.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Effect of various mutations in the GTPase and middle domain of Drp1 on the mitochondrial network, nucleoids, and peroxisomes
1Department of Paediatrics and Inherited Metabolic Disorders, Charles University and General University Hospital in Prague, Prague, Czech Republic; 2Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Importance of human ClpXP protease for mitochondrial function
First Faculty of Medicine, Charles University; and General University Hospital in Prague
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Ketogenic diet mitigates the pathogenic phenotype in TMEM70 deficient animal models
1Institute of Physiology of the Czech Acad. Sci., Prague, Czech Republic; 2Institute of Molecular Genetics of the Czech Acad. Sci., Prague, Czech Republic; 3Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mutation in Coq5 leads to CoQ10 deficiency, developmental delay and early death in zebrafish
1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs.Granada, Granada, Spain
[1] Malicdan MCV, Vilboux T, Ben-Zeev B, et al. A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-methyltransferase deficiency. Hum Mutat. 2018;39(1):69-79
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Omega-3 supplementation effects on mitochondrial and metabolic profile in a rabbit model of intrauterine growth restriction
1Inherited metabolic diseases and muscular disorders Lab, Cellex - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine and Health Science - University of Barcelona (UB), 08036 Barcelona, Spain; 2Internal Medicine Unit, Medicine Department, Hospital Clínic of Barcelona, 08036 Barcelona, Spain; 3Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain; 4BCNatal—Barcelona Centre for Maternal-Foetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), IDIBAPS, University of Barcelona, 08036 Barcelona, Spain; 5Department of Clinical Biochemistry, Institut de Recerca de Sant Joan de Deu, Esplugues de Llobregat, 08036 Barcelona, Spain
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Redundant and divergent roles of COQ8A and COQ8B in cell metabolism.
1Clinical Genetics Unit, Department of Women and Children’s Health, University of Padova and “Fondazione Istituto di Ricerca Pediatrica Città Della Speranza”, 35127 Padova, Italy.; 2Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, 70121 Bari, Italy; 3Department of Biomedical and Neuromotor Sciences, University of Bologna, I-40126 Bologna, Italy.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Loss of CHCHD8 (COA4) caused mitochondrial respiratory Complex IV deficiency
National Defense Academy, Japan
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Delving into the phenotypic heterogeneity of Coenzyme Q biosynthesis defects
1Centro Andaluz de Biología del Desarrollo/Universidad Pablo de Olavide-CSIC-JA, Seville, Spain; 2CIBERER, Instituto de Salud Carlos III, Madrid, Spain; 3Laboratorio de Fisiopatología Celular y Bioenergética, Seville, Spain.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Investigating the impact of mtDNA point mutations on mitochondrial function and bioenergetics using patient fibroblasts and hiPSC derived neuronal models
University College London, United Kingdom
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Human COQ10A and COQ10B genes are essential for Coenzyme Q function in mitochondrial respiration
1University of Padova, Italy; 2Isituto di Ricerca Pediatrica - Cittá della Speranza, Italy; 3Pablo de Olavide University, Sevilla, Spain
[1] Stefely JA, Pagliarini DJ. Biochemistry of Mitochondrial Coenzyme Q Biosynthesis. Trends Biochem Sci. 2017 Oct;42(10):824-843. doi: 10.1016/j.tibs.2017.06.008. Epub 2017 Sep 17. PMID: 28927698; PMCID: PMC5731490.
[2] Tsui HS, Pham NVB, Amer BR, Bradley MC, Gosschalk JE, Gallagher-Jones M, Ibarra H, Clubb RT, Blaby-Haas CE, Clarke CF. Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function. J Lipid Res. 2019 Jul;60(7):1293-1310. doi: 10.1194/jlr.M093534. Epub 2019 May 2. PMID: 31048406; PMCID: PMC6602128.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
The use of β-RA in leptin-deficient mice reveals novel mechanisms of this compound for the treatment of obesity
1Physiology Department, Biomedical Research Center, University of Granada, Granada, Spain; 2Ibs.Granada, Granada, Spain
Santos AL, Sinha S. Obesity and aging: Molecular mechanisms and therapeutic approaches. Ageing Res Rev. 2021;67:101268
Hidalgo-Gutiérrez A, Barriocanal-Casado E, Díaz-Casado ME, et al. β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight. Biomedicines. 2021;9(10):1457
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Oocyte-specific mitofusin 2 knockout enhances the metabolic disfunction of offspring born to obese mothers
Federal University of Sao Carlos, Brazil
GARCIA, B.M.; MACHADO, T.S.; CARVALHO, K.F.; NOLASCO, P.; NOCITI, R.P.; DEL COLLADO, M.; CAPO BIANCO, M.J.D.; GREJO, M.P.; AUGUSTO NETO, J.D.; SUGIYAMA, F.H.C.; TOSTES, K.; PANDEY, A.K.; GONÇALVES, L.M.; PERECIN, F.; MEIRELLES, F.V.; FERRAZ, J.B.S.; VANZELA, E.C.; BOSCHERO, A.C.; GUIMARÃES, F.E.G.; ABDULKADER, F.; LAURINDO, F.R. M.; KOWALTOWSKI, A.J.; CHIARATTI, M.R. Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis. Molecular Human Reproduction, v. 26, p. 938-952, 2020.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Off-target effects of etomoxir: inhibition of mitochondrial Complex I and fatty acid oxidation
1Oroboros Instruments, Innsbruck, Austria; 2Dept Biochem, Semmelweis Univ, Budapest, Hungary; 3CNC-Center Neurosci and Cell Biol, Univ Coimbra, Portugal; 4IIUC-Inst Interdisciplinary Research, Univ Coimbra, Portugal; 5CIBB-Center for Innovative Biomed Biotechnol, Univ Coimbra, Portugal; 6PDBEB-PhD Programme in Exp Biol Biomed, IIUC, Univ Coimbra, Portugal; 7Lab Pharmaceut Pharmacol, Latvian Inst Organic Synthesis, Riga, Latvia
Fischer C, Valente de Souza L, Komlódi T, Garcia-Souza LF, Volani C, Tymoszuk P, Demetz E, Seifert M, Auer K, Hilbe R, Brigo N, Petzer V, Asshoff M, Gnaiger E, Weiss G (2022) Mitochondrial respiration in response to iron deficiency anemia. Comparison of peripheral blood mononuclear cells and liver. https://doi.org/10.3390/metabo12030270
Komlódi T, Tretter L (2022) The protonmotive force – not merely membrane potential. Bioenerg Commun 2022.16. https://doi.org/10.26124/bec:2022-0016
Pallag G, Nazarian S, Ravasz D, Bui D, Komlódi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited. https://doi.org/10.3390/ijms23095111
Komlódi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. https://doi.org/10.26124/bec:2021-0003
Komlódi T, Sobotka O, Gnaiger E (2021) Facts and artefacts on the oxygen dependence of hydrogen peroxide production using Amplex UltraRed. https://doi.org/10.26124/bec:2021-0004
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Mitochondrial alterations in sirtuin1 heterozygous mice fed high fat diet and melatonin
1Dept Biomedical Sciences for Health, University of Milan, Milan, Italy; 2Laboratorio Morfologia Umana Applicata, IRCCS Policlinico San Donato, Milan, Italy; 3Dept Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 4Center for Electron Microscopy, University of Belgrade, Belgrade, Serbia; 5Instituto de Investigaciones Biomedicas “Alberto Sols” (CSIC-UAM), Madrid, Spain
1. Paramesha B. et al. Antioxidants (2021) 10: 338;
2. Stacchiotti A. et al. Cells (2019) 8: 1053.
3. Stacchiotti A et al. Nutrients (2017) 9:1323.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Microproteins in metabolic regulation
1Duke-NUS Medical School, Singapore; 2University of Melbourne, Australia; 3University of Utah, USA; 4University of Southampton, UK
Lena Ho, PhD (lead PI), is regarded as a pioneer in the field of microprotein research with over 30 primary research articles (5991 citations, H-index of 21) in top-tier journals. With more than 12 years of experience in microprotein discovery, functionalization and therapeutic development, Lena and her team have developed a framework of bioinformatic tools for mining ribo-seq data for disease-relevant small ORF peptides, as well as an extensive range of biochemical tools to validate their function and uncover their molecular mechanism. Lena is an EMBO Young Investigator and HHMI international scholar.
Recent publications :
1) Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity.
Lee CQE, Kerouanton B, Chothani S, Zhang S, Chen Y, Mantri CK, Hock DH, Lim R, Nadkarni R, Huynh VT, Lim D, Chew WL, Zhong FL, Stroud DA, Schafer S, Tergaonkar V, St John AL, Rackham OJL, Ho L. Nat Commun. 2021 Apr 9;12(1):2130. doi: 10.1038/s41467-021-22397-5.
2) Mitochondrial microproteins link metabolic cues to respiratory chain biogenesis.
Liang C, Zhang S, Robinson D, Ploeg MV, Wilson R, Nah J, Taylor D, Beh S, Lim R, Sun L, Muoio DM, Stroud DA, Ho L. Cell Rep. 2022 Aug 16;40(7):111204. doi: 10.1016/j.celrep.2022.111204.
3) Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly.
Zhang S, Reljić B, Liang C, Kerouanton B, Francisco JC, Peh JH, Mary C, Jagannathan NS, Olexiouk V, Tang C, Fidelito G, Nama S, Cheng RK, Wee CL, Wang LC, Duek Roggli P, Sampath P, Lane L, Petretto E, Sobota RM, Jesuthasan S, Tucker-Kellogg L, Reversade B, Menschaert G, Sun L, Stroud DA, Ho L.
4) Viral proteases activate the CARD8 inflammasome in the human cardiovascular system.
Nadkarni R, Chu WC, Lee CQE, Mohamud Y, Yap L, Toh GA, Beh S, Lim R, Fan YM, Zhang YL, Robinson K, Tryggvason K, Luo H, Zhong F, Ho L. J Exp Med. 2022 Oct 3;219(10):e20212117. doi: 10.1084/jem.20212117. Epub 2022 Sep 21.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Oxphos deficiency indicates novel functions for the mitochondrial protein import subunit tim50
1Department of Biochemistry and Pharmacology and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3010, Australia; 2Queensland Children’s Hospital, Department of Metabolic Medicine, South Brisbane, Brisbane, Queensland, 4001, Australia; 3Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia; 4Department of Paediatrics, University of Melbourne, Melbourne, Victoria, 3052, Australia; 5Victorian Clinical Genetics Services, Royal Children’s Hospital, Melbourne, Victoria, 3052, Australia
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
The levels and activation state of the pyruvate dehydrogenase complex modulate the SCAFI-dependent organization of the mitochondrial respiratory chain
1Instituto de Investigación Hospital 12 de Octubre, Madrid 28041, Spain; 2Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy; 3Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid, Spain
Fernández-Vizarra E, López-Calcerrada S, Sierra-Magro A, Pérez-Pérez R, Formosa LE, Hock DH, Illescas M, Peñas A, Brischigliaro M, Ding S, Fearnley IM, Tzoulis C, Pitceathly RDS, Arenas J, Martín MA, Stroud DA, Zeviani M, Ryan MT, Ugalde C. Two independent respiratory chains adapt OXPHOS performance to glycolytic switch. Cell Metab. 2022 Nov 1;34(11):1792-1808.e6. doi: 10.1016/j.cmet.2022.09.005. PMID: 36198313.
Modelling pathogenic mechanisms: OXPHOS, metabolic rewiring and tissue specificity
Development of a yeast model to characterize OPA1 mutations associated with different neuromuscular disorders
1Clinical Genetics Unit, Department of Women’s and Children’s Health, University of Padua, and Istituto di Ricerca Pediatrica (IRP) Città della Speranza, Padua, Italy; 2Department of Biomedical Sciences, University of Padua, Padua, Italy
Clinical 1: from new genes to old and novel phenotypes
An ultra-special family with an ultra-rare condition: three children with mithochondrial complex III deficiency due to homozygous mutations in Lyrm7
Bolzano Hospital, Italy
Invernizzi, Federica et al. “A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity.” Human mutation. 2013.
Sánchez E et al. LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial Complex III assembly in human cells. Biochim Biophys Acta. 2013.
Dallabona C. et al. LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance. Brain. 2016.
Hempel M. et al. LYRM7 - associated complex III deficiency: A clinical, molecular genetic, MR tomographic, and biochemical study. Mitochondrion. 2017.
Cherian A. et al. Multifocal cavitating leukodystrophy-A distinct image in mitochondrial LYRM7 mutations. Mult Scler Relat Disord. 2021.
Peruzzo R et al. Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction. Nat Commun. 2021.