The scaffolding and activation of NLRP3 on acidic vesicles depends on their biophysical properties and is independent of intermediate filaments

• DOI: 10.1091/mbc.e24-11-0511
• Publication Date: 2025-05-15T15:29:47Z
• Authors: Guillermo de Paz ...; Jan Mossemann; Blayne Sayed; Spencer A. Freeman
• Keywords: Pyroptosis; Organelle

Inflammasomes are nucleated by receptors that become activated upon cellular stresses including ionic dyshomeostasis. Rather than forming in the cytosol, recent evidence suggests inflammasomes at specific sites cell on cytoskeletal polymers and membrane surfaces of organelles. The NLRP3 inflammasome, which is formed loss cytosolic K + , had been proposed to form intermediate filaments as well vesicles along endocytic pathway. To determine necessary requirement either mechanism, we used vimentin knockout macrophages do not have compared formation function inflammasomes. We report was dispensable for activation caspase-1, IL-1β cleavage release, inflammatory responses mice attributed inflammasome. Instead, recruited PI(3,5)P2, PI(4)P- LAMP1-positive compartments undergoing osmotic swelling. Swelling these dependent V-ATPase, inhibition curtailed recruitment inflammasome activation. Similarly, decreasing hydrostatic pressure prevented recruitment, release pyroptosis. results suggest biophysical features acidic organelles [Media: see text]