Apoptotic protease activating factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis, which oligomerizes in response to cytochrome c release and forms a large complex known as apoptosome. At least six splice isoforms of Apaf-1 has been reported including Apaf-1S, Apaf-1XL, Apaf-1L, Apaf-1M, Apaf-1XS and Apaf-1ALT. Cytosolic cytochrome c binds to Apaf-1 protein, unraveling its closed auto-inhibited conformation. In response to cytochrome c binding and ADP exchange with ATP, Apaf-1 adopts a heptameric quaternary structure and thus recruits inactive procaspase-9 molecules.This mega Dalton complex, known as apoptosome, serves as an activation platform for the initiator procaspase-9 in the intrinsic pathway of apoptosis.Beside its fundamental role in the apoptotic cell death pathways, Apaf-1 has cell-cycle modulatory effect during DNA damage induced by genotoxic stress. Apaf-1 is involved in the DNA damage checkpoint in a phylogenetically conserved fashion and it seems to perform that independently from the activation of apoptotic effectors and Apaf-1 also participates in the centrosomal microtubule nucleation process, and cytoskeleton organization. 


1.Shakeri R,et al. Biochimie. 2017 Apr;135:111-125.