Chen Jian, You Chen, Xie Haibo, Zhu Qixing
Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Int J Biol Sci. 2025 Aug 22;21(12):5378-5392. doi: 10.7150/ijbs.119841. eCollection 2025.
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.
线粒体是细胞能量代谢和内环境稳态不可或缺的动态细胞器。除了其传统作用外，越来越多的证据强调线粒体作为先天免疫信号通路关键调节因子的重要性。最近，线粒体RNA（mtRNA）已被确定为炎症反应的一种新型调节因子。mtRNA被细胞内模式识别受体（PRR）检测到，随后激活线粒体抗病毒信号蛋白（MAVS）以及干扰素调节因子3（IRF3）/活化B细胞的核因子κB轻链增强子（NF-κB）信号轴，以及炎性小体途径。这种激活导致I型干扰素和促炎细胞因子的产生。此外，mtRNA通过外泌体介导的细胞间转移促进炎症信号的传播。在各种形式的mtRNA中，线粒体双链RNA（mt-dsRNA）由于其独特的双螺旋结构，特别容易激活炎症反应。mt-dsRNA的异常积累与自身免疫性疾病、退行性疾病、肝脏疾病、肾脏疾病、癌症、心血管疾病和呼吸系统疾病密切相关。本综述提出了创新的治疗策略，旨在通过靶向mtRNA代谢及其下游炎症过程中的关键调节节点来降解病理性mtRNA或中断炎症途径。
