Liu Song, Feng Min, Guan Wenxian
Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Int J Cancer. 2016 Aug 15;139(4):736-41. doi: 10.1002/ijc.30074. Epub 2016 Mar 25.
Recent studies have revealed the diverse pathophysiological functions of mitochondria beyond traditional energetic metabolism in cells. Mitochondria-released damage-associated molecular patterns, particularly mitochondrial deoxyribonucleic acid (mtDNA), play a central role in host immune defenses against foreign pathogens. Newly discovered cGAS-STING signaling is responsible for microbial DNA recognition, and potentially participates in mitochondrial DNA sensing. Inappropriate inflammatory signaling mediated by mtDNA is implicated in various human diseases, especially infectious/inflammatory disease and cancer. In addition, mtDNA horizontal transfer between tumor cells and surrounding somatic cells has been recently observed and been associated with tumorigenesis and cancer progression. In this review, we will summarize the molecular signaling of mtDNA recognition (especially STING signaling), and discuss the underlying mechanism by which mtDNA transfer triggers cancer progression in human. Besides, we will highlight the central role of mtDNA in host immunity, with particular emphasis on mtDNA-induced NETs (neutrophil extracellular traps) formation, apoptosis and autophagy.
最近的研究揭示了线粒体在细胞中除传统能量代谢之外的多种病理生理功能。线粒体释放的损伤相关分子模式，特别是线粒体脱氧核糖核酸（mtDNA），在宿主针对外来病原体的免疫防御中发挥核心作用。新发现的cGAS-STING信号传导负责微生物DNA识别，并可能参与线粒体DNA传感。由mtDNA介导的不适当炎症信号与多种人类疾病有关，尤其是感染性/炎症性疾病和癌症。此外，最近观察到肿瘤细胞与周围体细胞之间存在mtDNA水平转移，并与肿瘤发生和癌症进展相关。在这篇综述中，我们将总结mtDNA识别的分子信号传导（特别是STING信号传导），并讨论mtDNA转移触发人类癌症进展的潜在机制。此外，我们将强调mtDNA在宿主免疫中的核心作用，特别强调mtDNA诱导的中性粒细胞胞外陷阱（NETs）形成、凋亡和自噬。
