线粒体DNA与cGAS-STING固有免疫信号通路的研究前沿

线粒体是细胞中广泛存在的一种重要细胞器,除了管控细胞的能量制造和代谢外,线粒体还能参与细胞的抗感染、凋亡以及自噬等多种生物学过程.当外界环境或者细胞内部的有害刺激对线粒体造成应激反应时,线粒体会将包含其自身DNA(mitochondrial DNA,mtDNA)的线粒体基质释放到细胞质中.胞质内的mtDNA作为一种损伤...

Mitochondrial DNA and cGAS-STING Innate Immune Signaling Pathway: Latest Research Progress

Mitochondria are important organelles that present extensively in cells, serving diverse functions. In addition to controlling cell energy production and metabolism, mitochondria are also involved in various biological processes, including anti-infection, apoptosis, and autophagy. Harmful stimuli from external environment or those generated by the cells themselves can damage mitochondria and cause mitochondrial stress response, during which the mitochondrial matrix containing mitochondrial DNA (mtDNA) can leak into the cytoplasm. Cytoplasmic mtDNA, acting as a damage-associated molecular pattern (DAMP), can activate a panel of DNA sensors and elicit innate immune response in organisms. Cyclic GMP-AMP synthase (cGAS), a key intracellular DNA sensor, can catalyze the conversion of GTP and ATP to cyclic GMP-AMP (2′3′-cGAMP), which serves as second messenger to bind and activate stimulator of interferon gene (STING), an endoplasmic adaptor protein. Beyond its critical roles in anti-microbial immunity, cGAS-STING pathway also serves important functions in many pathological and physiological processes such as autoimmunity, tumor and senescence. In this review, we focus on how the mtDNA released during mitochonrial stress response activates the cGAS-STING innate immune signaling pathway and the associated diseases, in order to help promote basic research about the role of mitochondria in innate immunity and provide new strategies for developing mitochondria-targeting drugs.