The “fast” and the “slow” modes of mitochondrial DNA degradation

Abstract

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.

• Circulating mtDNA
• mtDNA repair
• mtDNA degradation
• oxidative mtDNA damage

Acknowledgements

The authors acknowledge Dr Rob Sobol for providing 92TAg cell line.

Declaration of interest

The authors declare no conflict of interest in the writing of this paper. These studies were supported by the National Institutes of Health grants ES03456, PO1 HL66299 and OD010944.