Mitochondrial diseases are a diverse group of inborn disorders affecting cellular energy production by oxidative phosphorylation (OXPHOS) via the five (CI‐CV) mitochondrial respiratory chain (MRC) complexes. The sea squirt alternative oxidase (AOX) is able to bypass the distal part of the MRC and was shown to alleviate the consequences of CIII and CIV defects in several cellular and Drosophila models. In this issue of EMBO Molecular Medicine, Rajendran et al (2019) demonstrate the first proof of concept in mammals, by showing that AOX is capable to extend lifespan and prevent heart failure in a CIII deficient mouse model, raising the possibility of future human AOX bypass treatment.
See also: J Rajendran et al (January 2019)
Mitochondria are intracellular organelles with a separate genome (mtDNA) and translation system, present in all enucleated cells. They are involved in numerous cellular pathways (intermediate metabolism, iron and calcium metabolism, cell death, etc.), but their main function is to provide cellular energy (ATP) via the mitochondrial respiratory chain (MRC), which is composed of ~89 proteins in five multimeric complexes (CI‐CV, with CI, CIII, CIV as super complexes) embedded in the mitochondrial inner membrane (IM). CI and CII transfer electrons from NADH and FADH2 originate from the tricarboxylic acid (TCA) to coenzyme Q (Q, ubiquinone). Q also …
