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Updated: Jul 11, 2025
Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Ming-Ming Hu1,2, Hong-Bing Shu3,4
1Department 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. mmhu@whu.edu.cn.
Abstract:
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.
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