Cytochrome c is a requisite component of the mitochondrial respiratory chain and participates in the electron transfer between complex III and complex IV of the respiratory chain. Cytochrome c is a soluble protein that is localized in the mitochondrial intermembrane space and is loosely attached to the surface of the inner membrane. The protein is synthesized on cytoplasmic ribosomes as apocytochrome c and then translocated into the mitochondria via a unique pathway independent of the general protein translocation machinery, protease-sensitive components of the outer membrane, or a membrane potential across the inner membrane. In response to a variety of apoptotic stimuli, cytochrome c is released from mitochondria into the cytosol. This release can be blocked by Bcl-2 and suggests that Bcl-2 may function by regulating cytochrome c release. Cytosolic cytochrome c is an essential component of the vertebrate apoptosome which is composed of cytochrome c, Apaf-1, and procaspase-9 (Apaf-3). Interaction of these proteins leads to the activation of caspase-9, which in turn activates other caspases (such as caspase-3) ultimately resulting in cell death. The current working hypothesis is that release of cytochrome c from mitochondria commits a cell to die either by a “rapid” apoptotic mechanism involving activation of the Apaf-1/caspase-9 cascade, or by a “slower” necrotic process involving the collapse of the electron transport chain.