Fig.4. The key role of mitochondria in eliciting an inflammatory response.
The mitochondria can serve as a signaling platform to control inflammation. Mitochondrial DNA (mtDNA) is released from damaged mitochondria into the cytosol through BCL2-associated X protein (BAX)/ BCL2-antagonist/killer (BAK), mitochondrial permeability transition pore (mPTP), or by mitochondria herniation. Cytosolic nucleotides are recognized by several nucleotide sensing pathways such as Cyclic GMP–AMP synthase (cGAS) - Stimulator of interferon genes (STING)- Interferon Regulatory Factor 3 (IRF3)/ IRF7, Retinoic acid-inducible gene I (RIG-I)/ Melanoma differentiation-associated protein 5 (MDA5)-Mitochondrial antiviral signaling protein (MAVS). These pathways activate pro-inflammatory genes including interferon-stimulated genes. Genetic deletion or pharmacological inhibitor of cGAS/STING or RIG-I attenuated kidney disease development.