Mitochondria as a regulator of inflammation. (Upper) Leakage of mitochondrial components. (a) Leaked N-formyl peptide binds to formyl peptide receptor (FPR) to activate NF-κB. (b) Leakage of mtDNA to the cytosol activates Toll-Like-Receptor (TLR), cyclic GMP-AMP synthase-simulator of interferon genes (cGAS-STING) pathways, and NLRP3 inflammasome. (c) ATP and cardiolipin activate NLRP3 inflammasome. (d) Mitochondrial ROS (mtROS) activates NLRP3 inflammasome and mitogen-activated protein kinase (MAPK) signaling. (e) Binding of mtDNA to cytosolic TFAM activates the TLR pathway. (f) Cytosolic cytochrome C (Cyt C) reduces IL-12 and increases lymphocyte cell death. (Lower) Regulation of inflammation pathway by mitochondrial factors. (g) MAVS recruits RIG-I or MDA5 to viral RNA to activate NF-κB and IRF3. (h) ESCIT generates mtROS by binding to TRAF6. (i) MARCH5 ubiquitinates TANK to enhance TRAF6 signaling.
