The Role of Mitochondrial DNA in the Development of Ischemia Reperfusion Injury

Abstract 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.