Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization

Cryo-electron tomography of NLRP3-activated ASC complexes reveals organelle co-localization

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Abstract NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation.Aberrant activity of NLRP3 occurs in many animed blue lotion topical spray 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 flexcon reverse osmosis water storage tank 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.