Cytochrome c is an essential component of the mitochondrial respiratory chain. It is a soluble protein, localized in the intermembrane space and loosely attached to the surface of the inner mitochondrial membrane. In response to a variety of apoptosis-inducing agents, cytochrome c is released from mitochondria to the cytosol (Kluck et al., 1997, Science, 275: 1132-36). The release of cytochrome c from the mitochondria during apoptosis precedes the mitochondrial deltaPSI disruption. In cells overexpressing Bcl-2 (or Bcl-XL) the release of cytochrome c is blocked, aborting the apoptotic response (Yang et al., 1997, Science, 275: 1129-1132).
Cytochrome c was found to be one essential component of the complex that induces Caspase-3 activation and apoptotic activity in cytoplasmic HeLa extracts upon dATP stimulation. Cytochrome c was suggested to mediate (together with dATP) the formation of the Apaf-1/Caspase-9 complex which results in activated Caspase-9. Caspase-9 is thought to trigger a caspase-cascade leading to apoptosis (Li et al., 1997, Cell, 91: 479-489).