![Figure 1. The intrinsic apoptosis pathway. In a healthy cell, prosurvival members (BCL2, BCL-XL, BCL2L2, MCL1, and BCL2A1) restrain the activity of prodeath BAK and BAX. Stress signals activate the BH3-only proteins, which overwhelm prosurvival proteins, thereby activating BAK and BAX. The latter oligomerizes and inserts into the outer mitochondrial membrane, causing permeabilization and release of cytochrome c from the mitochondria. This triggers formation of the apoptosome and subsequent activation of caspase-9, and the rest of the apoptotic caspase cascade. The extrinsic apoptosis pathway is induced upon ligand binding to death receptors (eg, FAS ligand [FasL] to FAS receptor). This initiates recruitment of adaptor proteins to the death receptor intracellular domain (death domain), which results in cleavage and activation of caspase-8. Active caspase-8 can directly activate the effector caspases, caspase-3 and caspase-7. In addition, it also can trigger the intrinsic pathway by cleaving BID to produce tBID, which then activates BAK and BAX. Professional illustration by Somersault18:24.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/131/6/10.1182_blood-2017-11-742684/4/blood742684f1.jpeg?Expires=1724936291&Signature=pJ-0-13cFbjxy9sG5OTszL~aH-GMH4bu-Wl2DeYo5td8WrqjESzeVfCUwx1-dABQdzhawSEahYbjl3htl8edqRztJKG0jTaQFK9ewyOvGO3oBMfneya1gnMkp0LurXq7v4~MTFVMYZX0INnL9Uenrx~KcTEhOtqr9ThtX-0SWrZZXOrZBu3osZb3UO9Db3vBWZ7oznMyf-BMsVaLCe8vtsVW6iAtgyx6BxZtZ7CCQV4tytheM8nSsMAmllixKj2JnWnz8bmiSGYApGq21aNal4PHjrluzQGJZU8ZM~G3GsQIcu6Bn6a1rrRm5exBZeKfswRi7VBSpqWGKC80OS1Fgg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
The intrinsic apoptosis pathway. In a healthy cell, prosurvival members (BCL2, BCL-XL, BCL2L2, MCL1, and BCL2A1) restrain the activity of prodeath BAK and BAX. Stress signals activate the BH3-only proteins, which overwhelm prosurvival proteins, thereby activating BAK and BAX. The latter oligomerizes and inserts into the outer mitochondrial membrane, causing permeabilization and release of cytochrome c from the mitochondria. This triggers formation of the apoptosome and subsequent activation of caspase-9, and the rest of the apoptotic caspase cascade. The extrinsic apoptosis pathway is induced upon ligand binding to death receptors (eg, FAS ligand [FasL] to FAS receptor). This initiates recruitment of adaptor proteins to the death receptor intracellular domain (death domain), which results in cleavage and activation of caspase-8. Active caspase-8 can directly activate the effector caspases, caspase-3 and caspase-7. In addition, it also can trigger the intrinsic pathway by cleaving BID to produce tBID, which then activates BAK and BAX. Professional illustration by Somersault18:24.
