Connected to Death: The (Unexpurgated) Mitochondrial Pathway of Apoptosis
Uli Maurer, and
Douglas R. Green
La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Fig. 1.. The vertebrate mitochondrial pathway of apoptosis. At the core of this pathway is the process of mitochondrial outer membrane permeabilization (MOMP). This is mediated predominantly by the proapoptotic Bcl-2 family members, Bax and Bak, and inhibited by the antiapoptotic Bcl-2 family proteins. The BH3-only proteins of this family regulate MOMP either by activating Bax and Bak (activators) or by antagonizing the antiapoptotic Bcl-2 proteins (derepressors). MOMP allows proteins of the mitochondrial intermembrane space to gain access to the cytosol. Cytochrome c triggers the activation of APAF-1, leading to formation of the apoptosome followed by recruitment and activation of caspase-9. Caspase-9, in turn, cleaves and activates the executioner caspases 3 and 7 to orchestrate apoptosis by the cleavage of key substrates. IAP inhibits caspase activation, and this inhibition can be reversed by IAP antagonists (for example, Smac and Omi) released from the mitochondria upon MOMP.
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