Liu, YangciYangciLiuZhai, HaomingHaomingZhaiAlemayehu, HelenHelenAlemayehuBoulanger, JérômeJérômeBoulangerHopkins, Lee JLee JHopkinsBorgeaud, Alicia CléaAlicia CléaBorgeaudHeroven, ChristinaChristinaHerovenHowe, Jonathan DJonathan DHoweLeigh, Kendra EKendra ELeighBryant, Clare EClare EBryantModis, YorgoYorgoModis2024-10-252024-10-252023-11-09https://boris-portal.unibe.ch/handle/20.500.12422/171272NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.en500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.48350/1887693794561210.1038/s41467-023-43180-8