Figure 1.

Diagram of the intrinsic and extrinsic apoptosis signaling pathways (adapted from ref. 80). Intrinsic apoptosis (left side) is usually the result of hypoxia, ischemia, or UV damage, but may also be induced via stress from low levels of growth factors. These damage signals are propagated through Casp2- and Trp53-mediated disruption of the mitochondrial membrane. Cytochrome c (Cycs) is released following mitochondrial membrane disruption and recruited to form the apoptosome with Apaf1 and pro-Casp9. Pro-Casp9 is cleaved and activates the caspase cascade resulting in cleavage and activation of Casp3, Casp6, and Casp7. The downstream effect of activation of the caspase cascade is DNA fragmentation, formation of apoptotic bodies, and cell death. The extrinsic apoptosis signaling pathway (right side) requires binding of the death ligand (FasL or TNF-α) to its respective receptor (FasR or Tnfrsf1b). Binding of the death ligand to the death signals the recruitment of Tradd, Fadd, and pro-Casp8. Pro-Casp8 is cleaved by the complex and begins the caspase cleavage cascade resulting in the cleavage and activation of Casp3, Casp6, and Casp7. Similar to the intrinsic pathway, the result of the caspase cleavage cascade is DNA fragmentation, formation of apoptotic bodies, and cell death.