Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, College of Life Sciences, Wuhan University, Research Unit of Innate Immune and Inflammatory Diseases, Chinese Academy of Medical Sciences, Wuhan, 430072, China.
Research Unit of Innate Immune and Inflammatory Diseases, Chinese Academy of Medical Sciences, Wuhan, 430072, China.
Cell Mol Immunol. 2023 Dec;20(12):1403-1412. doi: 10.1038/s41423-023-01086-x. Epub 2023 Nov 7.
Various cellular stress conditions trigger mitochondrial DNA (mtDNA) release from mitochondria into the cytosol. The released mtDNA is sensed by the cGAS-MITA/STING pathway, resulting in the induced expression of type I interferon and other effector genes. These processes contribute to the innate immune response to viral infection and other stress factors. The deregulation of these processes causes autoimmune diseases, inflammatory metabolic disorders and cancer. Therefore, the cGAS-MITA/STING pathway is a potential target for intervention in infectious, inflammatory and autoimmune diseases as well as cancer. In this review, we focus on the mechanisms underlying the mtDNA-triggered activation of the cGAS-MITA/STING pathway, the effects of the pathway under various physiological and pathological conditions, and advances in the development of drugs that target cGAS and MITA/STING.
各种细胞应激条件会触发线粒体 DNA(mtDNA)从线粒体释放到细胞质中。释放的 mtDNA 被 cGAS-MITA/STING 途径感知,导致 I 型干扰素和其他效应基因的诱导表达。这些过程有助于对病毒感染和其他应激因素的先天免疫反应。这些过程的失调会导致自身免疫性疾病、炎症代谢紊乱和癌症。因此,cGAS-MITA/STING 途径是干预感染、炎症和自身免疫性疾病以及癌症的潜在靶点。在这篇综述中,我们重点介绍了 mtDNA 触发 cGAS-MITA/STING 途径激活的机制、该途径在各种生理和病理条件下的作用,以及靶向 cGAS 和 MITA/STING 的药物开发的进展。