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

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