Pathways of apoptosis. The intrinsic apoptotic pathway is triggered when apoptotic stimuli stimulate proapoptotic proteins, such as Bax, to induce the permeabilization of the outer mitochondrial membrane, and the subsequent discharge of cytochrome c from the mitochondrial intermembranous space. Cytochrome c then participates in the formation of a multimeric Apaf-1/cytochrome c complex, which then forms the apoptosome by recruiting procaspase-9 in order to activate it. Once activated, caspase-9 is dissociated from this complex, and it activates executioner caspases-3, -6, and/or -7. On the other hand, extrinsic apoptotic pathway starts by trimerization of ligand-induced receptor subsequrnt to the binding of particular death ligands to death receptors. Subsequently, particular intracellular proteins that are associated with the death receptor, such as procaspase-8, are recruited. After its recruitment, procaspase-8 is immediately activated through proteolysis. Then the active caspase-9 and active caspase-8 cleave and activate downstream executioner caspases-3, 6, and/or 7 that carry out the proteolytic events of cellular proteins and structures ultimately leading to apoptosis.