Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310052, China.
Department of Pediatric Intensive Care Unit, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310052, China.
Chin Med J (Engl). 2024 May 5;137(9):1044-1053. doi: 10.1097/CM9.0000000000003022. Epub 2024 Mar 6.
Over the past decade, mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney disease. However, the precise molecular mechanisms linking mitochondrial damage to kidney disease remain elusive. The recent insights into the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthetase (cGAS)-stimulator of interferon gene (STING) signaling pathway have revealed its involvement in many renal diseases. One of these findings is that mitochondrial DNA (mtDNA) induces inflammatory responses via the cGAS-STING pathway. Herein, we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage, focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney diseases. Furthermore, we summarize the latest findings of cGAS-STING signaling pathway in cell, with a particular emphasis on its downstream signaling related to kidney diseases. This review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway, kidney diseases, and mitochondrial dysfunction.
在过去的十年中，线粒体功能障碍已被研究为导致急性和慢性肾病的关键因素。然而，将线粒体损伤与肾脏疾病联系起来的确切分子机制仍不清楚。最近对环鸟苷酸-腺苷酸（GMP-AMP）合成酶（cGAS）-干扰素基因刺激物（STING）信号通路的深入了解揭示了其在许多肾脏疾病中的作用。其中一个发现是线粒体 DNA（mtDNA）通过 cGAS-STING 通路诱导炎症反应。本文综述了线粒体损伤后 mtDNA 释放的机制，特别关注 mtDNA 释放激活的 cGAS-STING 信号与肾脏疾病发展之间的关联。此外，我们总结了 cGAS-STING 信号通路在细胞中的最新发现，特别强调与肾脏疾病相关的下游信号。这篇综述旨在增进我们对 cGAS-STING 通路、肾脏疾病和线粒体功能障碍之间复杂关系的理解。
