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

Author:

Scala Giovanni1,Ambrosio Susanna1,Menna Margherita1,Gorini Francesca2,Caiazza Carmen1,Cooke Marcus S3,Majello Barbara1,Amente Stefano2ORCID

Affiliation:

1. Department of Biology, University of Naples Federico II , 80138  Naples , Italy

2. Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II , 80131  Naples , Italy

3. Oxidative Stress Group, Department of Molecular Biosciences, University of South Florida , Tampa, FL 33620 , USA

Abstract

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.

Funder

Programma per il Finanziamento della Ricerca di Ateneo Linea A

National Center for Gene Therapy and Drugs

AIRC

National Institute of Environmental Health Sciences of the National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Applied Mathematics,Computer Science Applications,Genetics,Molecular Biology,Structural Biology

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