Figure 2.

Intrinsic and extrinsic apoptotic activation. Activation of the apoptotic program can occur intrinsically when cells sense internal damage and stress leading to activation of the proapoptotic BH3-only BCL-2 family members. The BH3-only proteins prevent anti-apoptotic BCL-2-like proteins from inhibiting Bak/Bax oligomerization on the OMM. Once oligomerized, proapoptotic factors like Cyt c escape into the cytosol and activate caspase-3 via the Apaf-1 apoptosome. Extrinsic apoptotic activation occurs when death ligands bind to cell surface death receptors leading to the recruitment and activation of pro-caspase-8. Active caspase-8 can then directly activate caspase-3 to begin dismantling the cell or cleave BID to activate the intrinsic apoptotic pathway.