Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

doi:10.1002/JLB.MR0318-124R

Review

. 2019 Feb;105(2):377-399.

doi: 10.1002/JLB.MR0318-124R. Epub 2018 Dec 27.

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Monica Yabal¹, Dale J Calleja², Daniel S Simpson^{2

3}, Kate E Lawlor^{4

5}

Affiliations

¹ III. Medical Department for Hematology and Oncology, Kinikum rechts der Isar, Technische Universität München, Munich, Germany.
² The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
³ Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Hudson Institute of Medical Research, Clayton, Victoria, Australia.
⁵ Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia.

PMID: 30589456
DOI: 10.1002/JLB.MR0318-124R

Review

Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

Monica Yabal et al. J Leukoc Biol. 2019 Feb.

. 2019 Feb;105(2):377-399.

doi: 10.1002/JLB.MR0318-124R. Epub 2018 Dec 27.

Authors

Monica Yabal¹, Dale J Calleja², Daniel S Simpson^{2

3}, Kate E Lawlor^{4

5}

Affiliations

¹ III. Medical Department for Hematology and Oncology, Kinikum rechts der Isar, Technische Universität München, Munich, Germany.
² The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
³ Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
⁴ Hudson Institute of Medical Research, Clayton, Victoria, Australia.
⁵ Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia.

PMID: 30589456
DOI: 10.1002/JLB.MR0318-124R

Abstract

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.

Keywords: caspases; inflammasome; metabolism; mitochondria; reactive oxygen species.

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Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

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Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

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