Pyroptosis, a form of programmed inflammatory cell death, is mechanistically distinguished from classical apoptosis by:
- A Caspase-3/7 activation causing DNA ladder formation and membrane blebbing without plasma membrane rupture
- B Gasdermin D cleavage by caspase-1/4/5/11 generating N-terminal pore-forming fragments that rupture the plasma membrane and release IL-1beta and IL-18 ✓
- C RIP3-MLKL pathway causing MLKL phosphorylation, oligomerization, and plasma membrane disruption without caspase activation
- D Cytochrome c release from mitochondria activating Apaf-1 and the apoptosome to activate executioner caspases
Explanation
Pyroptosis is a form of regulated inflammatory cell death executed by the gasdermin family. Upon inflammasome activation (e.g., NLRP3, NLRC4), caspase-1 (canonical) or caspase-4/5/11 (non-canonical) cleave gasdermin D, liberating the N-terminal pore-forming domain. These N-terminal fragments oligomerize and insert into the plasma membrane, forming pores that disrupt osmotic balance, cause membrane rupture, and release pre-formed IL-1beta, IL-18, and DAMPs. This distinguishes pyroptosis from apoptosis (caspase-3/7, DNA ladder, intact membrane) and necroptosis (RIP3-MLKL pathway, no gasdermin involvement). The mitochondrial pathway described is the intrinsic apoptosis pathway.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.