The power of life-Cytochrome c oxidase takes center stage in metabolic control, cell signalling and survival

Mitochondrial dysfunction is increasingly recognized as a major factor in the etiology and progression of numerous human diseases, such as (neuro-)degeneration, ischemia reperfusion injury, cancer, and diabetes. Cytochrome c oxidase (COX) represents the rate-limiting enzyme of the mitochondrial respiratory chain and is thus predestined for being a central site of regulation of oxidative phosphorylation, proton pumping efficiency, ATP and reactive oxygen species production, which in turn affect cell signaling and survival. A unique feature of COX is its regulation by various factors and mechanisms interacting with the nucleus-encoded subunits, whose actual functions we are only beginning to understand.