In the intrinsic pathway of apoptosis, cytochrome c released from mitochondria binds to which adaptor protein to form the apoptosome, leading to activation of which initiator caspase?
- A FADD — activates caspase-8
- B TRADD — activates caspase-10
- C CARD domain of RIP1 — activates caspase-2
- D Apaf-1 — activates caspase-9 ✓
Explanation
In the intrinsic (mitochondrial) pathway, pro-apoptotic signals cause BAX/BAK-mediated mitochondrial outer membrane permeabilisation (MOMP) releasing cytochrome c into the cytosol. Cytochrome c binds Apaf-1 (apoptotic protease activating factor-1), which oligomerises with dATP/ATP into the heptameric apoptosome. The apoptosome recruits and activates procaspase-9 (the initiator caspase of this pathway), which then cleaves and activates executioner caspases-3 and -7. FADD and caspase-8 belong to the extrinsic (death receptor) pathway. Bcl-2/Bcl-xL inhibit MOMP and are therefore anti-apoptotic.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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