It is well-known that mitochondrial DNA (mtDNA) can escape to intracellular or extracellular compartments under different stress conditions, yet understanding their escape mechanisms remains a challenge. Although Bax/Bak pores and VDAC oligomers are the strongest possibilities, other mechanisms may be involved. For example, mitochondria permeability transition, altered mitophagy, and mitochondrial dynamics are associated with intracellular mtDNA escape, while extracellular traps and extracellular vesicles can participate in extracellular mtDNA escape. The evidence suggests that mtDNA escape is a complex event with more than one mechanism involved. In addition, once the mtDNA is outside the mitochondria, the effects can be complex. Different danger signal sensors recognize the mtDNA as a damage-associated molecular pattern, triggering an innate immune inflammatory response that can be observed in multiple metabolic diseases characterized by chronic inflammation, including autoimmune diseases, diabetes, cancer, and cardiovascular disorders. For these reasons, we will review the most recent evidence regarding mtDNA escape mechanisms and their impact on different metabolic diseases.

众所周知，线粒体DNA（mtDNA）可以在不同的胁迫条件下逃逸至细胞内或细胞外区室，但了解其逃逸机制仍然是一个挑战。尽管Bax / Bak孔和VDAC低聚物是最强的可能性，但可能涉及其他机制。例如，线粒体通透性转变，线粒体改变和线粒体动力学与细胞内mtDNA逃逸有关，而细胞外陷阱和细胞外囊泡可以参与细胞外mtDNA逃逸。有证据表明，mtDNA逃逸是一个复杂的事件，涉及多个机制。此外，一旦mtDNA位于线粒体之外，其作用可能很复杂。不同的危险信号传感器将mtDNA识别为与损伤相关的分子模式，触发先天性免疫炎症反应，这种疾病可以在多种以慢性炎症为特征的代谢疾病中观察到，包括自身免疫性疾病，糖尿病，癌症和心血管疾病。由于这些原因，我们将回顾有关mtDNA逃逸机制及其对不同代谢疾病的影响的最新证据。