Mitochondrial respiratory chain complex IV (Complex IV (also known as COX))

Mitochondrial respiratory chain complex IV, also known as **cytochrome c oxidase** (COX), is the terminal enzyme of the mitochondrial electron transport chain. It catalyzes the transfer of electrons from reduced cytochrome c to molecular oxygen, reducing it to water. This process is coupled with pumping protons across the inner mitochondrial membrane, contributing to an electrochemical gradient used by ATP synthase for ATP production. Complex IV consists of multiple subunits—three core subunits encoded by mitochondrial DNA and additional nuclear DNA–encoded subunits—which together form a large metalloprotein assembly embedded in the inner mitochondrial membrane. The activity and assembly of this complex are tightly regulated; defects or inhibition can result in severe metabolic diseases such as Leigh syndrome and have been implicated in cancer, neurodegeneration, cardiovascular diseases, and other pathologies. Complex IV is also a central regulatory site for oxidative phosphorylation; its function can be modulated by steroids, thyroid hormones, phosphorylation events on its subunits, lipid environment changes, and small molecule inhibitors.

Other names

Cytochrome c oxidaseCOXElectron transport chain complex IVRespiratory chain complex IV

Inhibition of electron transfer and proton pumping by direct binding to the enzyme or interference with proton translocation pathways