Mitochondria: commanders of innate immunity and disease?

► Update on the current literature supporting mitochondria as master regulators of the following innate immune signaling pathways. ► TLR; the mitochondrial proteins MARCH5, ECSIT and SMAC/DIABLO directly regulate TLR innate immune signaling. ► RLR;Mitochondrial proteins MAVS, TOM70, STING, NLRX1, gC1qR, MFN1/2 regulate RLR signaling from positions on outer mitochondrial membrane. ► NLR; mtDNA and mROS activate NLRP3 inflammasome. Activation also relies on the mitochondrial proteins VDAC, TXNIP and ATP (OXPHOS). ► Role of mitochondrial metabolism (glucose, glutamine, fatty acids, amino acids and mitophagy) controlling innate immune signaling pathways.