Phosphorylation of OXPHOS Machinery Subunits: Functional Implications in Cell Biology and Disease

The complexes of the electron transport chain and ATP synthase comprise the oxidative phosphorylation (OXPHOS) system. The reactions of OXPHOS generate the mitochondrial membrane potential, drive the majority of ATP production in respiring cells, and contribute significantly to cellular reactive oxygen species (ROS). Regulation of OXPHOS is therefore critical to maintain cellular homeostasis. OXPHOS machinery subunits have been found to be highly phosphorylated, implicating this post-translational modification as a means whereby OXPHOS is regulated. Multiple lines of evidence now reveal the diverse mechanisms by which phosphorylation of OXPHOS machinery serve to regulate individual complex stability and activity as well as broader cellular functions. From these mechanistic studies of OXPHOS machinery phosphorylation, it is now clear that many aspects of human health and disease are potentially impacted by phosphorylation of OXPHOS complexes. This mini-review summarizes recent studies that provide robust mechanistic detail related to OXPHOS subunit phosphorylation.