Liu, Yangci; Zhai, Haoming; Alemayehu, Helen; Boulanger, Jérôme; Hopkins, Lee J; Borgeaud, Alicia C; Heroven, Christina; Howe, Jonathan D; Leigh, Kendra E; Bryant, Clare E; Modis, Yorgo (2023). Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization. Nature communications, 14(1), p. 7246. Nature Publishing Group 10.1038/s41467-023-43180-8
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Borgeaud, Alicia Cléa |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
14 Nov 2023 16:30 |
Last Modified: |
26 Nov 2023 02:26 |
Publisher DOI: |
10.1038/s41467-023-43180-8 |
PubMed ID: |
37945612 |
BORIS DOI: |
10.48350/188769 |
URI: |
https://boris.unibe.ch/id/eprint/188769 |
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