The role of mitochondria in NLRP3 inflammasome activation.

By Qiuyu Liu, Danyan Zhang, D. Hu, Xiangmei Zhou, Yang Zhou. Molecular Immunology, 2018

1,466 citations recorded by the source corpus.

The NLRP3 inflammasome is a multiprotein platform which is activated upon cellular infection or stress. Its activation leads to caspase-1-dependent secretion of proinflammatory cytokines like interleukin-1β (IL-1β) and IL-18, and an inflammatory form of cell death termed as pyroptosis. Recent studies have unveiled the pivotal roles of mitochondria in initiation and regulation of the NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3) inflammasome. NLRP3 activators induce mitochondrial destabilization, NLRP3 deubiquitination, linear ubiquitination of ASC, and externalization or release of mitochondria-derived molecules such as cardiolipin and mitochondrial DNA. These molecules bind to NLRP3 that is translocated on mitochondria and activate the NLRP3 inflammasome. Here we review recently described mechanisms by which mitochondria regulate NLRP3 inflammasome activation.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ae33856cc8591cec4107b69f2b2458bcd797d44c

How researchers see this paper

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In Immunology

1. T. Kanneganti
2. G. Núñez
3. H. Hara
4. Rongbin Zhou
5. Yuan He
6. Shizuo Akira
7. M. Lamkanfi
8. J. Tschopp

In Molecular Biology

1. T. Kanneganti
2. G. Núñez
3. Yuan He
4. D. Sharma
5. H. Hara
6. Wei Jiang
7. J. K. Kim
8. H. D. Alexander

Citations in the corpus

• NLRP3 inflammasome activation and cell death (2021, background): “Together with several other groups, we found that Bcl-2 inhibited classical agonist- and Zika virus infection-mediated NLRP3 inflammasome activation by regulating mitochondrial homeostasis and VDAC activity but had no effect on salmonellamediated IPAF inflammasome activation [42, 135, 136].”
• NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component (2015, neutral): “Lys NLRP3 ASC WT K64M WT (1) Nek7 +/+ (GFP) (2) Nek7 (GFP) (3) Nek7 (GFP + NEK7) (4) Nek7 (GFP + NEK7(K64M))”
• Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. (2018, background): “ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome in macrophages [15].”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “Zhou and colleagues identified that mitochondrial ROS was involved in the activation of NLRP3 (58).”
• Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders (2017, background): “Mitochondria damage, represented as mitochondria fission, clustering and reactive oxygen species production, is proposed as an upstream signaling event of NLRP3 activation (Zhou et al., 2011).”
• The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation (2016, background): “Production of reactive oxygen species (ROS), potassium efflux, changes in cell volume, calcium signaling, and lysosomal disruption have all been proposed as critical upstream signals required for NLRP3 activation (Cruz et al., 2007; Pétrilli et al., 2007; Cassel et al., 2008; Dostert et al., 2008; H”
• An update on the regulatory mechanisms of NLRP3 inflammasome activation (2021, background): “Indeed, NLRP3 signaling activators result in mitochondrial destabilization and the release of mitochondria-derived molecules, such as mtDNA and cardiolipin, to further activate the NLRP3 inflammasome complex.(124,130,136) Circulating mitochondrial DAMPs, including formyl peptides and mtDNA, can be p”
• Mechanism and regulation of NLRP3 inflammasome activation (2016, background): “The implication of mitochondrial dysfunction in NLRP3 activation was originally based on chemical inhibitors in which the perturbation of mitochondria were found to promote activation of the NLRP3 inflammasome [48].”