ALIX mediates reversible gasdermin-D pore formation via the endosomal pathway to limit pyroptosis by active membrane repair.

ABSTRACT: Pyroptosis is a form of regulatory cell death characterized by membrane rupture and release of pro-inflammatory signals. In pyroptosis, Caspase-1 activation leads to the cleavage of gasdermin-D (GSDMD). Upon cleavage, GSDMD's N-terminal (N-GSDMD) fragments insert into the plasma membrane, oligomerize, and form pores. The molecular details that define whether GSDMD pore formation results in cell death or survival are largely unknown. In this study, we show that a shorter duration of membrane N-GSDMD pores (t ≤ 2 h), along with associated membrane permeability does not harm cellular viability. We demonstrate that N-GSDMD is removed, and membrane integrity is restored if the pyroptotic stimulus is washed out within 1 hour. In contrast, longer duration of N-GSDMD pore formation leads to large-

SUBMITTER: Otchere S 

PROVIDER: S-EPMC12501301 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature