Come on mtDNA, light my fire

Oxidized mitochondrial DNA (ox-mtDNA) activates NLRP3 inflammasome signaling through an ill-defined mechanism. In this issue of Immunity, Xian et al. reveal FEN1 endonuclease cleaves ox-mtDNA into fragments that escape mitochondria, igniting NLRP3 and cGAS-STING signaling and inflammation.

Automated summary

In this study, the researchers uncover the role of FEN1 endonuclease in the cleavage of oxidized mitochondrial DNA, leading to the activation of NLRP3 and cGAS-STING signaling pathways and subsequent inflammation.