The activation of caspases is a key regulatory step in apoptosis. Once cytochrome c is released from the mitochondria into the cytosol, it binds Apaf-1 to form an oligomeric cytochrome c/Apaf-1 complex, which induces caspase activation. Inhibitors of Apoptosis Proteins (IAPs), are a family of proteins that regulate the cytochrome c/Apaf-1 caspase activating pathway. Like cytochrome c, Smac (for second mitochondria-derived activator of caspase, also designated DIABLO in mouse for direct IAP binding protein with low PI) promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway by binding IAPs and preventing them from inhibiting caspases. In healthy cells, Smac is a mitochondrial protein, but when cells undergo apoptosis, Smac is released into the cytosol.
