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Nucleic Acids Research Advance Access published online on March 5, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp100
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome Integrity, Repair and Replication

Oxidative stress induces degradation of mitochondrial DNA

Inna Shokolenko, Natalia Venediktova, Alexandra Bochkareva, Glenn L. Wilson and Mikhail F. Alexeyev*

Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, AL 36688, USA

*To whom correspondence should be addressed. Tel: +1 251 460 6789; Fax: +1 251 460 6771; Email: malexeye{at}jaguar1.usouthal.edu

Received September 4, 2008. Revised January 25, 2009. Accepted February 8, 2009.

Mitochondrial DNA (mtDNA) is located in close proximity of the respiratory chains, which are the main cellular source of reactive oxygen species (ROS). ROS can induce oxidative base lesions in mtDNA and are believed to be an important cause of the mtDNA mutations, which accumulate with aging and in diseased states. However, recent studies indicate that cumulative levels of base substitutions in mtDNA can be very low even in old individuals. Considering the reduced complement of DNA repair pathways available in mitochondria and higher susceptibility of mtDNA to oxidative damage than nDNA, it is presently unclear how mitochondria manage to maintain the integrity of their genetic information in the face of the permanent exposure to ROS. Here we show that oxidative stress can lead to the degradation of mtDNA and that strand breaks and abasic sites prevail over mutagenic base lesions in ROS-damaged mtDNA. Furthermore, we found that inhibition of base excision repair enhanced mtDNA degradation in response to both oxidative and alkylating damage. These observations suggest a novel mechanism for the protection of mtDNA against oxidative insults whereby a higher incidence of lesions to the sugar–phosphate backbone induces degradation of damaged mtDNA and prevents the accumulation of mutagenic base lesions.


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