During the intrinsic pathway of apoptosis, Bax/Bak form pores in the outer mitochondrial membrane. What is the DIRECT consequence that commits the cell to apoptosis?
- A Loss of mitochondrial membrane potential and ATP depletion
- B Release of cytochrome c forming the apoptosome with Apaf-1 and procaspase-9 ✓
- C Activation of caspase-8 via DISC (death-inducing signaling complex)
- D Nuclear translocation of NF-kB
Correct answer: B. Release of cytochrome c forming the apoptosome with Apaf-1 and procaspase-9
Explanation
Bax/Bak pores allow cytochrome c release from the intermembrane space into the cytoplasm. Cytochrome c binds Apaf-1, inducing conformational change and recruitment of 7 Apaf-1/cytochrome-c units to form the heptameric apoptosome, which recruits and activates procaspase-9. Active caspase-9 then cleaves and activates executioner caspases 3 and 7, committing the cell to apoptosis. Caspase-8 activation via DISC is the extrinsic pathway; NF-kB activation is anti-apoptotic.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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