Which of the following pairs of initiator caspase and its activation platform is correct for the extrinsic (death receptor) pathway of apoptosis?

• A Caspase-9 activated at the apoptosome assembled by Apaf-1 and cytochrome c
• B Caspase-8 activated at the DISC assembled by FADD upon death receptor ligation ✓
• C Caspase-3 activated directly by tumor necrosis factor receptor clustering
• D Caspase-12 activated by the inflammasome and gasdermin D pores

Explanation

In the extrinsic pathway, engagement of Fas or TNF receptors leads to recruitment of FADD and procaspase-8 into the death-inducing signaling complex (DISC), where caspase-8 is activated and then cleaves executioner caspases 3 and 7. Option A describes the intrinsic mitochondrial pathway, where cytochrome c and Apaf-1 form the apoptosome to activate caspase-9. Caspase-3 is an executioner caspase and cannot be activated directly by receptor clustering without upstream initiator caspases.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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