The two major pathways of apoptosis. The intrinsic or mitochondrial pathway of apoptosis (left) involves mitochondrial dysfunction, release of cytochromec(cyt c), and the subsequent activation of caspase 9 (casp-9) at the apoptosome. The antiapoptotic protein B-cell lymphoma 2 (Bcl-2) inhibits the release of cytochrome c from the mitochondrion. The extrinsic or death receptor pathway (right) is initiated by binding of death ligands to their cognate death receptors and subsequent recruitment of the adapter protein Fas-associated protein with death domain (FADD) and caspase 8 (casp-8) into the death-inducing signaling complex (DISC). Both apoptosis pathways converge at the activation of effector caspase 3 (casp-3), which cleaves several cellular proteins, finally leading to the typical alterations of apoptosis such as DNA fragmentation. Fas = fibroblast-associated receptor; TNF-R = tumor necrosis factor receptor.