Function and dysfunction of the oxidative phosphorylation system

The key energy source in a cell is the high-energy compound ATP, which is mainly generated by oxidative phosphorylation (OXPHOS). The mammalian OXPHOS system comprises five large membrane complexes, which are believed to be organised in higher order assemblies, supercomplexes. The complexes are built from numerous polypeptide subunits and prosthetic groups and their biosynthesis is a complicated process that requires both nuclear and mitochondrial gene products. Many genetic defects can occur that cause improper function of the OXPHOS system and a decrease in ATP production, but also can lead to an increase of toxic reactive oxygen species. Recent advances have revealed new structural components and components of the assembly machinery of the OXPHOS system. This review describes the components of the OXPHOS system, their organisation, proteins involved in their biogenesis, and mutations in these components, which have been described to affect OXPHOS function leading to disorders.