Shokolenko Inna N, Wilson Glenn L, Alexeyev Mikhail F
a Department of Cell Biology and Neuroscience , University of South Alabama , Mobile , AL , USA.
Mitochondrial DNA A DNA Mapp Seq Anal. 2016;27(1):490-8. doi: 10.3109/19401736.2014.905829. Epub 2014 Apr 14.
In a living cell, oxidative stress resulting from an external or internal insult can result in mitochondrial DNA (mtDNA) damage and degradation. Here, we show that in HeLa cells, mtDNA can withstand relatively high levels of extracellular oxidant H2O2 before it is damaged to a point of degradation, and that mtDNA levels in these cells quickly recover after removal of the stressor. In contrast, mtDNA degradation in mouse fibroblast cells is induced at eight-fold lower concentrations of H2O2, and restoration of the lost mtDNA proceeds much slower. Importantly, mtDNA levels in HeLa cells continue to decline even after withdrawal of the stressor thus marking the "slow" mode of mtDNA degradation. Conversely, in mouse fibroblasts maximal loss of mtDNA is achieved during treatment, and is already detectable at 5 min after exposure, indicating the "fast" mode. These differences may modulate susceptibility to oxidative stress of those organs, which consist of multiple cell types.
在活细胞中，由外部或内部损伤引起的氧化应激可导致线粒体DNA（mtDNA）损伤和降解。在此，我们表明，在HeLa细胞中，mtDNA在被损伤至降解点之前能够承受相对高水平的细胞外氧化剂过氧化氢（H2O2），并且在去除应激源后这些细胞中的mtDNA水平会迅速恢复。相比之下，小鼠成纤维细胞中的mtDNA降解在过氧化氢浓度低八倍时就会被诱导，并且丢失的mtDNA的恢复过程要慢得多。重要的是，HeLa细胞中的mtDNA水平即使在去除应激源后仍会继续下降，从而标志着mtDNA降解的“缓慢”模式。相反地，在小鼠成纤维细胞中，mtDNA在处理过程中会出现最大程度的丢失，并且在暴露后5分钟就已可检测到，这表明是“快速”模式。这些差异可能会调节由多种细胞类型组成的那些器官对氧化应激的易感性。
