Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization.
Publisher DOI
PubMed ID
37945612
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, 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.
Date Issued
2023-11-09
Publication Type
Article
Language(s)
en
Author(s)
Liu, Yangci | |
Zhai, Haoming | |
Alemayehu, Helen | |
Boulanger, Jérôme | |
Hopkins, Lee J | |
Heroven, Christina | |
Howe, Jonathan D | |
Leigh, Kendra E | |
Bryant, Clare E | |
Modis, Yorgo |
Additional Credits
Journal
Nature communications
Publisher
Nature Publishing Group
ISSN
2041-1723
Access(Rights)
open.access