Departamento de Bioquímica e Biologia Tecidual, UNICAMP, Campinas, SP, Brazil.
Departamento de Bioquímica, Instituto de Ciências Biomédicas, UNIFAL, Alfenas, MG, Brazil.
Exp Parasitol. 2020 Dec;219:108016. doi: 10.1016/j.exppara.2020.108016. Epub 2020 Oct 6.
Different genotoxic agents can lead to DNA single- and double-strand breaks, base modification and oxidation. As most living organisms, Trypanosoma cruzi is subjected to oxidative stress during its life cycle; thus, DNA repair is essential for parasite survival and establishment of infection. The mitochondrion plays important roles beyond the production of ATP. For example, it is a source of signaling molecules, such as the superoxide anion and HO. Since T. cruzi has only one mitochondrion, the integrity of this organelle is pivotal for parasite viability. HO and methyl methanesulfonate cause DNA lesions in T. cruzi that are repaired by different DNA repair pathways. Herein, we evaluate mitochondrial involvement during the repair of nuclear and mitochondrial DNA in T. cruzi epimastigotes incubated with these two genotoxic agents under conditions that induce repairable DNA damage. Overall, in both treatments, an increase in oxygen consumption rates and in mitochondrial HO release was observed, as well as maintenance of ATP levels compared to control. Interestingly, these changes coincided with DNA repair kinetics, suggesting the importance of the mitochondrion for this energy-consuming process.
不同的遗传毒性试剂可导致 DNA 单链和双链断裂、碱基修饰和氧化。作为大多数生物，克氏锥虫在其生命周期中会受到氧化应激；因此，DNA 修复对于寄生虫的存活和感染的建立至关重要。线粒体除了产生 ATP 之外，还具有重要作用。例如，它是信号分子的来源，如超氧阴离子和 HO。由于克氏锥虫只有一个线粒体，因此该细胞器的完整性对寄生虫的生存能力至关重要。HO 和甲基甲磺酸酯可引起克氏锥虫的 DNA 损伤，这些损伤可通过不同的 DNA 修复途径进行修复。在此，我们评估了在诱导可修复性 DNA 损伤的条件下，用这两种遗传毒性试剂孵育的克氏锥虫前鞭毛体中，线粒体在修复核 DNA 和线粒体 DNA 过程中的参与情况。总的来说，在两种处理中，均观察到耗氧率和线粒体 HO 释放增加，并且与对照相比，ATP 水平得以维持。有趣的是，这些变化与 DNA 修复动力学一致，表明线粒体对于这个耗能过程的重要性。
