ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation

TLDR

Pyroptosis is an inflammatory cell death triggered by caspase‑mediated cleavage of gasdermin D into pore‑forming fragments, yet many cells with active inflammasomes resist this death. ESCRT‑III is recruited to the plasma membrane following GSDMD activation, where its repair activity limits cytokine release and pyroptosis. Rühl et al., Science, p.

Abstract

Fine-tuning pyroptosis with ESCRT-III Pyroptosis is an inflammatory form of cell death induced by select caspases downstream of inflammasome complexes. These caspases cleave gasdermin D (GSDMD), whose N-terminal fragments quickly form large permeability pores that induce cell death. However, a large percentage of cells with active inflammasomes are resistant to pyroptosis. Rühl et al. found that the membrane-remodeling ESCRT-III machinery was recruited to the plasma membrane upon GSDMD activation. ESCRT-III–dependent membrane repair limited proinflammatory cytokine secretion and pyroptosis after activation of inflammasomes. Science , this issue p. 956