Mitochondrial RNA in Inflammation

Mitochondria are dynamic organelles integral to cellular energy metabolism and homeostasis. Beyond their traditional roles, a growing body of evidence underscores the importance of mitochondria as pivotal regulators of innate immune signaling pathways. Recently, mitochondrial RNA (mtRNA) has been identified as a novel modulator of inflammatory responses. mtRNA is detected by intracellular pattern recognition receptors (PRRs), which subsequently activate the mitochondrial antiviral-signaling protein (MAVS) and the interferon regulatory factor 3 (IRF3)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling axis, as well as inflammasome pathways. This activation leads to the production of type I interferons and pro-inflammatory cytokines. Furthermore, mtRNA facilitates the propagation of inflammatory signals through exosome-mediated intercellular transfer. Among the various forms of mtRNA, mitochondrial double-stranded RNA (mt-dsRNA) is particularly prone to activating inflammatory responses due to its distinctive double-helical structure. The aberrant accumulation of mt-dsRNA is strongly linked autoimmune diseases, degenerative disease, Liver Disease, kidney disease, cancers, cardiovascular diseases, and respiratory ailments. This review proposes innovative therapeutic strategies aimed at degrading pathological mtRNA or interrupting inflammatory pathways by targeting critical regulatory nodes in mtRNA metabolism and its downstream inflammatory processes.