Figure 3.

Mitochondrial regulation of NLRP3 inflammasome activation and mitochondrial DAMP activity. The NLRP3 inflammasome is activated by signals including mitochondrial reactive oxygen species (ROS), oxidised mitochondrial DNA (ox-mtDNA) and potassium efflux through the ATP-gated channel P2X7. Components of the inflammasome localise to mitochondrial and ER membranes upon activation, where they associate with MAVS, Mfn 2 and cardiolipin in the outer mitochondria membrane. Oligomerised NLRP3 and its adapter protein ASC recruit and activate caspase-1, which cleaves gasdermin D and interleukin-1 family cytokines into their active forms. Ox-mtDNA also exhibits DAMP activity by stimulating other pattern recognition receptors including the endosomal toll-like receptor TLR9.