Cytochrome c oxidase (COX) functions as the terminal oxidase of the respiratory chain that uses cytochrome c as an electron donor to drive a proton gradient across the inner mitochondrial membrane. The mammalian COX apoenzyme is a heteromer consisting of three mitochondrial encoded catalytic subunits and several nuclear gene encoded structural subunits. COX contains two iron-coordination sites and two copper-coordination sites. Cytochrome c oxidase IV (COX4) is a nuclear-encoded subunit of COX that may play a role in regulating COX activity. COX4 is expressed ubiquitously in adult human tissue with the strongest levels of expression in the pancreas and moderate expression levels in heart, skeletal muscle and placenta.