Fernandez-Vizarra 2013 Abstract IOC80

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Fernandez-Vizarra E (2013) Testing OXPHOS biogenesis and function in mitochondrial disease models. Mitochondr Physiol Network 18.09.

Link: IOC80 Schroecken

Fernandez-Vizarra E, Reyes A, Viscomi C, Zeviani M (2013)

Event: MiPNet18.09 IOC80

Our laboratory is mainly interested in the discovery of new genes whose mutations cause oxidative phosphorylation (OXPHOS) defects in human tissues, leading to mitochondrial disease syndromes. Once a candidate mutant gene is identified, usually by linkage or NGS analysis, our aim is to validate the pathogenic role of the mutation and understand the molecular mechanism linking the variant protein to faulty OXPHOS and disease. This goal can be achieved by studying tissue samples obtained from the patients, usually muscle biopsies and cultured fibroblasts from skin biopsies. Additionally, knocked-down expression of the candidate gene product can be achieved by RNAi technology applied to cultured cell lines. Furthermore, mouse knock-out models for the gene of interest can eventually be generated to gain deeper understanding of the biochemical and pathophysiological effects associated with the lack of the protein in living tissues, and whole organism. To test OXPHOS functionality in this wide spectrum of tissues and cells from patients as well as in the ad hoc recombinant models, we will perform oxygen consumption measurements in basal conditions and on exposure to specific substrates and inhibitors. This first characterization will provide key information to then continue with the analyses of physical status of OXPHOS-related complexes and their individual activities.

Keywords: Mitochondrial Respiratory Chain assembly disorders


Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression  Pathology: Myopathy, Neurodegenerative, Other  Stress:Mitochondrial disease  Organism: Human, Mouse  Tissue;cell: Other cell lines 



HRR: Oxygraph-2k 


Affiliation

MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, CB2 0XY Cambridge, UK.