Which event commits a cell irreversibly to the intrinsic (mitochondrial) pathway of apoptosis?

• A Activation of caspase-8 by the death-inducing signaling complex
• B Translocation of cytochrome c to the cytosol and apoptosome formation ✓
• C Phosphorylation of BH3-only proteins by survival kinases
• D Expression of anti-apoptotic Bcl-2 on the mitochondrial membrane

Explanation

Once cytochrome c escapes through BAX-BAK pores and binds APAF-1 to form the apoptosome, which activates caspase-9, the executioner caspases are engaged and the commitment is irreversible. Caspase-8 activation belongs to the extrinsic pathway, not the intrinsic one. Anti-apoptotic Bcl-2 actually blocks mitochondrial permeabilization, so its expression opposes apoptosis. BH3-only protein phosphorylation by survival kinases such as Akt is an inhibitory event upstream of commitment.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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