Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Lab for Trauma and Surgical Infection, Nanjing, China.
Shock. 2019 Jan;51(1):52-59. doi: 10.1097/SHK.0000000000001190.
Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures that can lead to multiple organ failure and high mortality in critically ill patients. Mitochondria are often considered the cellular power factory via their capacity for ATP generation. Recently, mitochondria have been further identified as vital regulators of cell death, inflammation, and oxidative stress, all of which can aggravate I/R injury. Studies have indicated that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and aggravates I/R injury. mtDNA is emerging as an agonist of the innate immune system that influences inflammatory pathology during I/R injury. In addition, when mtDNA is released into the cytoplasm, extracellular milieu, or circulation, it can activate multiple pattern-recognition receptors to trigger type I interferon and pro-inflammatory responses. Here, we review the emerging role of mtDNA in I/R injury to highlight novel mechanistic insights and discuss the pathophysiological relevance of mitochondrial biology.
缺血/再灌注（I/R）损伤是一种常见的病症，主要发生在急性肠系膜缺血、创伤或感染性休克、烧伤和外科手术中，可导致重症患者多器官衰竭和高死亡率。线粒体通常被认为是细胞的能量工厂，因为它们具有产生 ATP 的能力。最近，线粒体进一步被确定为细胞死亡、炎症和氧化应激的重要调节因子，所有这些都会加重 I/R 损伤。研究表明，线粒体 DNA（mtDNA）损伤导致线粒体功能障碍，从而加重 I/R 损伤。mtDNA 作为先天免疫系统的激动剂出现，影响 I/R 损伤期间的炎症病理。此外，当 mtDNA 释放到细胞质、细胞外环境或循环中时，它可以激活多种模式识别受体，触发 I 型干扰素和促炎反应。在这里，我们综述了 mtDNA 在 I/R 损伤中的新作用，以突出新的机制见解，并讨论线粒体生物学的病理生理相关性。
