APAF1
MIM.602233 HGNC:576
Cytochrome c (CYCS) (MIM.123970) released from the mitochondrial intermembrane space triggers a major caspase activation cascade through the cytochrome c/APAF1/CASP9 pathway.
Cytochrome c is located in the mitochondria of all aerobic cells and is involved in the electron transport system that functions in oxidative phosphorylation. It accepts electrons from cytochrome b and transfers them to cytochrome oxidase. In the process, the iron of the heme group, which is identical to that of hemoglobin and myoglobin, shifts from the ferrous to the ferric state.
Upon its release to the cytosol, cytochrome c (CYCS) binds to APAF1 (MIM.602233) in the presence of dATP or ATP. The cytochrome c/APAF1 complex then recruits procaspase-9 (CASP9) (MIM.602234), inducing its autoactivation and leading to the activation of downstream caspases (CSPs).
Proteins of the BCL2 (MIM.603167) families and inhibitor of apoptosis proteins (IAPs) are major regulators of the cytochrome c/APAF1/CASP9 pathway. SMAC (Diablo) promotes caspase activation in this pathway.