Mitochondrial DNA in NLRP3 inflammasome activation

As an intracellular polyprotein complex, the NLRP3 inflammasome is activated by NLRP3 perceiving pathogen-related molecular patterns, damage-related molecular patterns(DAMPs), which will result in the secretion of the caspase1-dependent pro-inflammatory cytokines IL1β and IL18, and the cleavage of GSDMD-mediated pyroptosis. Therefore, inflammasome signaling is tightly regulated. Intracellular and extracellular mitochondria DNA (mtDNA) play different roles in activating the NLRP3 inflammasome. Intracellular mtDNA is easily oxidized and transferred to the cytoplasm, and directly binds to NLRP3 to activate NLRP3 inflammasome, the extracellular mtDNA is involved in the priming and activation of NLRP3 inflammasome as a DAMP; which is related to the occurrence and development of plentiful diseases. In this paper, we will discuss how mitochondrial DNA activates the NLRP3 inflammasome and how the process of activating NLRP3 inflammasome by mtDNA interacts with other NLRP3 inflammasome activation models.