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Title | Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 7246, Year 2023 |
Publish date | Nov 9, 2023 |
Authors | Yangci Liu / Haoming Zhai / Helen Alemayehu / Jérôme Boulanger / Lee J Hopkins / Alicia C Borgeaud / Christina Heroven / Jonathan D Howe / Kendra E Leigh / Clare E Bryant / Yorgo Modis / |
PubMed Abstract | NLRP3 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, ...NLRP3 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. |
External links | Nat Commun / PubMed:37945612 / PubMed Central |
Methods | EM (tomography) |
Structure data | EMDB-13586: Cryo-electron tomography of ASC signalling sites in pyroptotic cells (2) |
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