Cancer Research UK Beatson Institute, Glasgow, UK.
Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
EMBO Rep. 2020 Apr 3;21(4):e49799. doi: 10.15252/embr.201949799. Epub 2020 Mar 23.
Mitochondria are cellular organelles that orchestrate a vast range of biological processes, from energy production and metabolism to cell death and inflammation. Despite this seemingly symbiotic relationship, mitochondria harbour within them a potent agonist of innate immunity: their own genome. Release of mitochondrial DNA into the cytoplasm and out into the extracellular milieu activates a plethora of different pattern recognition receptors and innate immune responses, including cGAS-STING, TLR9 and inflammasome formation leading to, among others, robust type I interferon responses. In this Review, we discuss how mtDNA can be released from the mitochondria, the various inflammatory pathways triggered by mtDNA release and its myriad biological consequences for health and disease.
线粒体是细胞器官,它们协调着从能量产生和代谢到细胞死亡和炎症等广泛的生物学过程。尽管存在这种看似共生的关系,但线粒体内部却隐藏着先天免疫的有效激动剂:它们自己的基因组。线粒体 DNA 释放到细胞质中并进入细胞外环境,会激活多种不同的模式识别受体和先天免疫反应,包括 cGAS-STING、TLR9 和炎性小体形成,导致强烈的 I 型干扰素反应等。在这篇综述中,我们讨论了 mtDNA 如何从线粒体中释放出来,mtDNA 释放引发的各种炎症途径及其对健康和疾病的众多生物学后果。