In the intrinsic (mitochondrial) pathway of apoptosis, which event is the CRITICAL initiating step that commits the cell to death?
- A Mitochondrial outer membrane permeabilization (MOMP) with cytochrome c release ✓
- B Activation of caspase-8 by FADD
- C Cleavage of PARP by effector caspases
- D Phosphatidylserine externalization on the plasma membrane
Correct answer: A. Mitochondrial outer membrane permeabilization (MOMP) with cytochrome c release
Explanation
In the intrinsic pathway, pro-apoptotic BAX and BAK oligomerize at the outer mitochondrial membrane in response to cellular stress, forming pores that allow cytochrome c release. Cytochrome c then binds APAF-1 to form the apoptosome, activating caspase-9 and the effector caspases. MOMP is the point of no return. Caspase-8 activation is the initiating event in the extrinsic (death-receptor) pathway.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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