Cytochrome c oxidase: Evolution of control via nuclear subunit addition

► OXPHOS allowscells to produce more ATP but also toxic elements such as ROS and NADH. ► Success of endosymbiosis has depended on the regulation of endosymbiont OXPHOS. ► Cytochrome c oxidase (COX) is a key regulator of OXPHOS. ► Addition of nuclear subunits controlling mitochondrial subunits marks COX evolution. ► COX control function is an as yet under-appreciated key point of evolution.