Accumulation of 8-oxodG within the human mitochondrial genome positively associates with transcription.

Abstract

Mitochondrial DNA (mtDNA) can be subject to internal and environmental stressors that lead to oxidatively generated damage and the formation of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxodG). The accumulation of 8-oxodG has been linked to degenerative diseases and aging, as well as cancer. Despite the well-described implications of 8-oxodG in mtDNA for mitochondrial function, there have been no reports of mapping of 8-oxodG across the mitochondrial genome. To address this, we used OxiDIP-Seq and mapped 8-oxodG levels in the mitochondrial genome of human MCF10A cells. Our findings indicated that, under steady-state conditions, 8-oxodG is non-uniformly distributed along the mitochondrial genome, and that the longer non-coding region appeared to be more protected from 8-oxodG accumulation compared with the coding region. However, when the cells have been exposed to oxidative stress, 8-oxodG preferentially accumulated in the coding region which is highly transcribed as H1 transcript. Our data suggest that 8-oxodG accumulation in the mitochondrial genome is positively associated with mitochondrial transcription.