Cytochrome C

Cytochrome c is a well characterized mobile electron transport protein that is essential to energy conversion in all aerobic organisms. In mammalian cells, this highly conserved protein is normally localized to the mitochondrial intermembrane space. More recent studies have identifed cytosolic cytochrome c as a factor necessary for activation of apoptosis. During apoptosis, cytochrome c is translocated from the mitochondrial membrane to the cytosol, where it is required for activation of caspase-3 (CPP32). Overexpression of Bcl-2 has been shown to prevent the translocation of cytochrome c, thereby blocking the apoptotic process. Overexpression of Bax has been shown to induce the release of cytochrome c and to induce cell death. The release of cytochrome c from the mitochondria is thought to trigger an apoptotic cascade, whereby Apaf-1 binds to Apaf-3 (caspase-9) in a cytochrome c-dependent manner, leading to caspase-9 cleavage of caspase-3.