Pyroptosis is a form of programmed inflammatory cell death that differs from apoptosis. Which molecular mechanism is the DEFINING feature of pyroptosis?
- A Cytochrome c release activating caspase-9
- B Gasdermin D cleavage by caspase-1 or caspase-11, creating membrane pores and releasing IL-1β and IL-18 ✓
- C RIPK3-mediated phosphorylation of MLKL causing membrane rupture
- D Caspase-8 activation via death receptors (extrinsic pathway)
Correct answer: B. Gasdermin D cleavage by caspase-1 or caspase-11, creating membrane pores and releasing IL-1β and IL-18
Explanation
Pyroptosis is a lytic, pro-inflammatory cell death executed primarily through inflammasome activation (NLRP3, AIM2, NLRC4) which cleaves caspase-1, which in turn cleaves gasdermin D (GSDMD). The N-terminal fragment of GSDMD oligomerizes and inserts into the plasma membrane, forming pores (15-20 nm diameter) that cause osmotic lysis and release of IL-1β, IL-18, and DAMPs. This differs from apoptosis (which is non-inflammatory and uses caspase-3/9) and necroptosis (which uses RIPK3/MLKL). Pyroptosis is important in defense against intracellular pathogens.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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