Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation

Billingham, Leah K.; Stoolman, Joshua S.; Vasan, Karthik; Rodriguez, Arianne E; Poor, Taylor A.; Szibor, Marten; Jacobs, Howard T.; Reczek, Colleen R.; Rashidi, Aida; Zhang, Peng; Miska, Jason; Chandel, Navdeep S.

doi:10.1038/s41590-022-01185-3

articleNature ImmunologyApr 28, 2022HYBRID OA

Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation

LKLeah K. Billingham JSJoshua S. Stoolman KVKarthik Vasan AEArianne E Rodriguez TATaylor A. Poor

Northwestern University · Tampere University · +3 more institutions

PubMed

Indexed incrossrefdatacitepubmed

Abstract

The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the NLRP3 inflammasome through several mechanisms including generation of mitochondrial reactive oxygen species (ROS). Here, we report that mitochondrial electron transport chain (ETC) complex I, II, III and V inhibitors all prevent NLRP3 inflammasome activation. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI1) or Ciona intestinalis alternative oxidase, which can complement the functional loss of mitochondrial complex I or III, respectively, without generation of ROS, rescued NLRP3 inflammasome…

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326

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Topics & keywords

Topics

Keywords

Inflammasome
Mitochondrial ROS
Mitochondrion
Cell biology
Reactive oxygen species
Biology
Bioenergetics
Chemistry

UN Sustainable Development Goals

Life in Land

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