Pathology · Cell Injury, Death and Adaptations (Apoptosis, Necrosis, Free Radicals)

Pyroptosis is a form of programmed cell death distinct from apoptosis and necroptosis. It is triggered by inflammasome activation. Which effector protein of pyroptosis directly executes membrane pore formation?

  • A Gasdermin D (GSDMD) N-terminal fragment
  • B RIPK3-MLKL complex
  • C Caspase-3 activated PARP cleavage
  • D Perforin released from activated cytotoxic T cells
Correct answer: A. Gasdermin D (GSDMD) N-terminal fragment

Explanation

In pyroptosis, activated inflammatory caspases (caspase-1 after NLRP3/NLRP1 inflammasome activation; caspase-4/5 after cytosolic LPS sensing) cleave gasdermin D, releasing the N-terminal domain (GSDMD-NT) from autoinhibition. GSDMD-NT oligomerises and inserts into the plasma membrane, forming large pores (~20 nm) that cause osmotic swelling, membrane rupture, and release of mature IL-1β and IL-18. MLKL oligomerisation and membrane insertion executes necroptosis (downstream of RIPK3), while caspase-3 mediates apoptosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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