Pyroptosis is a form of programmed cell death distinct from apoptosis and necrosis. Which of the following best describes the molecular mechanism of gasdermin-D mediated pyroptosis?
- A Caspase-1/4/5/11 cleaves gasdermin-D; N-terminal fragment forms membrane pores causing osmotic lysis with IL-1β/IL-18 release ✓
- B Gasdermin-D directly activates BAX/BAK on mitochondria causing MOMP and cytochrome c release
- C Gasdermin-D activates RIPK3-MLKL complex causing necroptotic membrane disruption
- D Gasdermin-D is cleaved by caspase-3/7 causing DNA fragmentation identical to apoptosis
Correct answer: A. Caspase-1/4/5/11 cleaves gasdermin-D; N-terminal fragment forms membrane pores causing osmotic lysis with IL-1β/IL-18 release
Explanation
Pyroptosis is inflammasome-dependent programmed necrosis. Activated caspase-1 (canonical, via NLRP3/AIM2/NLRC4 inflammasomes) or caspase-4/5 (human) / caspase-11 (mouse) (non-canonical, recognizing cytosolic LPS) cleave gasdermin-D into N-terminal and C-terminal fragments. The N-terminal fragment oligomerizes and inserts into plasma and mitochondrial membranes, forming large pores (10-20 nm), causing osmotic imbalance, cell lysis, and release of pre-formed IL-1β and IL-18. This is distinct from necroptosis (RIPK3-MLKL) and apoptosis (caspase-3/7).
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.