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.
Keywords: Calcium; Cardiolipin; Reactive oxygen species; Ubiquitination; mtDNA.
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