Bcl-2 family members and permeabilization of the outer mitochondrial membrane

Mitochondria play a major role in many apoptotic responses. They coordinate caspase activation through the release of cytochrome c and DIABLO/Smac as a result of the outer mitochondrial membrane becoming permeable. The release of these proteins is controlled by Bcl-2 family members. The mechanisms whereby Bcl-2 family members control the permeability of the outer mitochondrial membrane are still unclear. Apoptosis is an essential process required for the development and maintenance of tissue homeostasis. increased apoptosis could contribute to neurodegenerative diseases. Central components of the death machinery include the Bcl-2, apoptotic protease-activating factor-1 (Apaf-1) and caspase family members. The caspases are cysteine proteases that cleave key intracellular substrates, resulting in the morphological and biochemical changes associated with apoptosis. Recently, it was found that, in many apoptotic responses, caspase activation is coordinated by mitochondria.