Fig. 1.

The role of the Bcl-2 family of proteins in apoptosis. 1 The extrinsic pathway is activated by Fas ligand or TRAIL, subsequently activating caspase 8. 2 Caspase 8 transforms Bid into truncated Bid (tBid). In addition, caspase 8 initiates a cascade of caspase activation. 3 Diverse forms of extracellular stress, (DNA damage, cytotoxic drugs, and cytokine withdrawal) initiate the intrinsic pathway. 4 BH3-only proteins (Bim, Bid, Bad, Noxa, and Puma) engage with antiapoptotic Bcl-2 family proteins (Bcl-2, Bcl-XL, Bcl-w, and Mcl-1) to relieve their inhibition of Bax and Bak to activate them. 5 Bax and Bak are oligomerized and activated, leading to mitochondrial outer membrane permeabilization (MOMP). 6 Once mitochondrial membranes are permeabilized, cytochrome c is released into the cytoplasm, resulting in activation of caspase 9, subsequently caspase 3, which is the initiation step for the cascade of caspase activation