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Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation
Author(s) -
Yabal Monica,
Calleja Dale J.,
Simpson Daniel S.,
Lawlor Kate E.
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.mr0318-124r
Subject(s) - inflammasome , pyroptosis , biology , microbiology and biotechnology , mitochondrion , inflammation , programmed cell death , caspase 1 , nod , immunology , apoptosis , biochemistry , gene
Inflammasomes are multimeric protein complexes that induce the cleavage and release of bioactive IL‐1β and cause a lytic form of cell death, termed pyroptosis. Due to its diverse triggers, ranging from infectious pathogens and host danger molecules to environmental irritants, the NOD‐like receptor protein 3 (NLRP3) inflammasome remains the most widely studied inflammasome to date. Despite intense scrutiny, a universal mechanism for its activation remains elusive, although, recent research has focused on mitochondrial dysfunction or potassium (K + ) efflux as key events. In this review, we give a general overview of NLRP3 inflammasome activation and explore the recently emerging noncanonical and alternative pathways to NLRP3 activation. We highlight the role of the NLRP3 inflammasome in the pathogenesis of metabolic disease that is associated with mitochondrial and oxidative stress. Finally, we interrogate the mechanisms proposed to trigger NLRP3 inflammasome assembly and activation. A greater understanding of how NLRP3 inflammasome activation is triggered may reveal new therapeutic targets for the treatment of inflammatory disease.