Mitochondrial disorders of the OXPHOS system

Fernandez-Vizarra, E. and Zeviani, M. (2021) Mitochondrial disorders of the OXPHOS system. FEBS Letters, 595(8), pp. 1062-1106. (doi: 10.1002/1873-3468.13995) (PMID:33159691)

Abstract

Mitochondrial disorders are among the most frequent inborn errors of metabolism, their primary cause being the dysfunction of the oxidative phosphorylation system (OXPHOS). OXPHOS is composed of the electron transport chain (ETC), formed by four multimeric enzymes and two mobile electron carriers, plus an ATP synthase [also called complex V (cV)]. The ETC performs the redox reactions involved in cellular respiration while generating the proton motive force used by cV to synthesize ATP. OXPHOS biogenesis involves multiple steps, starting from the expression of genes encoded in physically separated genomes, namely the mitochondrial and nuclear DNA, to the coordinated assembly of components and cofactors building each individual complex and eventually the supercomplexes. The genetic cause underlying around half of the diagnosed mitochondrial disease cases is currently known. Many of these cases result from pathogenic variants in genes encoding structural subunits or additional factors directly involved in the assembly of the ETC complexes. Here, we review the historical and most recent findings concerning the clinical phenotypes and the molecular pathological mechanisms underlying this particular group of disorders.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fernandez-Vizarra, Dr Erika
• Authors: Fernandez-Vizarra, E., and Zeviani, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: FEBS Letters
• Publisher: Wiley
• ISSN: 0014-5793
• ISSN (Online): 1873-3468
• Published Online: 07 November 2020
• Copyright Holders: Copyright © 2020 Federation of European Biochemical Societies
• First Published: First published in FEBS Letters 595(8): 1062-1106
• Publisher Policy: Reproduced in accordance with the publisher copyright policy