Saki Mohammad, Prakash Aishwarya
Mitchell Cancer Institute, The University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, United States.
Mitchell Cancer Institute, The University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36604, United States.
Free Radic Biol Med. 2017 Jun;107:216-227. doi: 10.1016/j.freeradbiomed.2016.11.050. Epub 2016 Nov 30.
The electron transport chain is the primary pathway by which a cell generates energy in the form of ATP. Byproducts of this process produce reactive oxygen species that can cause damage to mitochondrial DNA. If not properly repaired, the accumulation of DNA damage can lead to mitochondrial dysfunction linked to several human disorders including neurodegenerative diseases and cancer. Mitochondria are able to combat oxidative DNA damage via repair mechanisms that are analogous to those found in the nucleus. Of the repair pathways currently reported in the mitochondria, the base excision repair pathway is the most comprehensively described. Proteins that are involved with the maintenance of mtDNA are encoded by nuclear genes and translocate to the mitochondria making signaling between the nucleus and mitochondria imperative. In this review, we discuss the current understanding of mitochondrial DNA repair mechanisms and also highlight the sensors and signaling pathways that mediate crosstalk between the nucleus and mitochondria in the event of mitochondrial stress.
电子传递链是细胞产生ATP形式能量的主要途径。该过程的副产物会产生活性氧，从而可能导致线粒体DNA受损。如果DNA损伤未得到妥善修复，其积累会导致线粒体功能障碍，进而引发包括神经退行性疾病和癌症在内的多种人类疾病。线粒体能够通过类似于细胞核中的修复机制来对抗氧化性DNA损伤。在目前已报道的线粒体修复途径中，碱基切除修复途径是描述最为全面的。参与线粒体DNA维持的蛋白质由核基因编码，并转运至线粒体，这使得细胞核与线粒体之间的信号传递至关重要。在本综述中，我们讨论了目前对线粒体DNA修复机制的理解，并强调了在发生线粒体应激时介导细胞核与线粒体之间相互作用的传感器和信号通路。
