The intrinsic apoptotic pathway is initiated by stress signals that alter mitochondrial membrane permeability and induce the release of apoptogenic factors such as cytochrome c and Smac/DIABLO. Mitochondrial membrane permeabilization is regulated by a balance of the apposing actions of pro-apoptotic and anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-XL, Bim, Bax, Bak, etc). The release of cytochrome c triggers the formation of the apoptosome; a protein complex containing caspase-9, APAF-1 and cytochrome c. Activated caspase-9 will activate caspase-3, -7 to induce apoptosis.
Figure 2: Schematic of the intrinsic pathway (mitochondrial-mediated).