Mitochondria, and apoptosis

Mitochondria and Apoptosis The loss of mitochondrial integrity is a major route initiating apoptosis (see Chapter 18, section V). The intermembrane space contains procaspases —2, —3, and 9, which are proteolytic enzymes that are in the zymogen form (i.e., must be proteolytically cleaved to be active). It also contains apoptosis initiating factor (AIF) and caspase-activated DNAase (CAD). Cytochrome c, which is loosely bound to the outer mitochondrial membrane, may also enter the intermembrane space when the electrochemical potential gradient is lost. The release of cytochrome c and the other proteins into the cytosol initiates apoptosis. 

Green DR, Reed JC. Mitochondria and apoptosis. Science 1998 281 1309-1312. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997 91(4) 479-489. 

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