Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death

Trends Biochem Sci. 2017 Apr;42(4):245-254. doi: 10.1016/j.tibs.2016.10.004. Epub 2016 Dec 5.


Pyroptosis was long regarded as caspase-1-mediated monocyte death in response to certain bacterial insults. Caspase-1 is activated upon various infectious and immunological challenges through different inflammasomes. The discovery of caspase-11/4/5 function in sensing intracellular lipopolysaccharide expands the spectrum of pyroptosis mediators and also reveals that pyroptosis is not cell type specific. Recent studies identified the pyroptosis executioner, gasdermin D (GSDMD), a substrate of both caspase-1 and caspase-11/4/5. GSDMD represents a large gasdermin family bearing a novel membrane pore-forming activity. Thus, pyroptosis is redefined as gasdermin-mediated programmed necrosis. Gasdermins are associated with various genetic diseases, but their cellular function and mechanism of activation (except for GSDMD) are unknown. The gasdermin family suggests a new area of research on pyroptosis function in immunity, disease, and beyond.

Keywords: caspase; gasdermin; innate immunity; necrosis; pore-forming protein; pyroptosis.

Publication types

  • Review

MeSH terms

  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Necrosis / metabolism*
  • Neoplasm Proteins / metabolism*
  • Phosphate-Binding Proteins
  • Pyroptosis*


  • GSDMD protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Phosphate-Binding Proteins