Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico.
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico; Centro de Investigación Biomédica, Hospital Zambrano-Hellion, San Pedro Garza García, Nuevo León, Mexico.
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165761. doi: 10.1016/j.bbadis.2020.165761. Epub 2020 Mar 10.
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）在不同的应激条件下可以逃到细胞内或细胞外隔室，但了解其逃逸机制仍然是一个挑战。虽然 Bax/Bak 孔和 VDAC 寡聚体是最强的可能性，但其他机制也可能参与其中。例如，线粒体通透性转换、改变的线粒体自噬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 逃逸是一个涉及多种机制的复杂事件。此外，一旦 mtDNA 逃出线粒体，其影响可能是复杂的。不同的危险信号传感器将 mtDNA 识别为损伤相关分子模式，触发先天免疫炎症反应，这种反应可以在多种以慢性炎症为特征的代谢性疾病中观察到，包括自身免疫性疾病、糖尿病、癌症和心血管疾病。基于这些原因，我们将回顾关于 mtDNA 逃逸机制及其对不同代谢性疾病影响的最新证据。
