1. Caspase Activation Intrinsic Pathway
SIGMA-ALDRICH
Cytochrome c is released from the mitochondria of pre-apoptotic cells and binds to Apaf-1 in the presence of dATP/ATP. The interaction results in a conformational change in Apaf-1 allowing the molecules of Apaf-1 to associate with each other. This formation results in a wheel-like structure that contains 7 molecules each of Apaf-1, cytochrome c and ATP. Pro-Caspase-9 contains a caspase recruitment domain (CARD) that is used to mediate specific interactions with Apaf-1 CARD, which becomes exposed on the apoptosome during assembly. Pro-Caspase-9 is autoactivated and after cleavage, mature caspase-9 remains bound to the apoptosome where it is able to activate executioner caspases such as caspase-3 and caspase-7.