Figure 8: Promotion of caspase activation by caspase-9-mediated feedback amplification of mitochondrial damage. Various stress signals promote the release of Smac and cytochrome c from the mitochondria to promote the activation of caspase-9. (A) Without caspase-mediated feedback disruption of the mitochondria through cleavage of anti-apoptotic Bcl-2 family proteins, members of the IAP family inhibit the full activation of caspases and thus the execution of apoptosis. (B) Caspase-mediated cleavage of antiapoptotic Bcl-2 family proteins promotes the complete disruption of the outer mitochondrial membrane, furthering the release Smac and cytochrome c. Complete release of Smac and cytochrome c results in the full activation of caspases and apoptosis.