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What causes mitochondrial DNA deletions in human cells?

Nature Genetics volume 40, pages 275–279 (2008)Cite this article

Abstract

Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central role in the aging of postmitotic tissues. Understanding the mechanism of the formation and subsequent clonal expansion of these mtDNA deletions is an essential first step in trying to prevent their occurrence. We review the previous literature and recent results from our own laboratories, and conclude that mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process.

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Figure 1: Diagram illustrating the proposed methods of mtDNA replication.
Figure 2: Diagram illustrating the previously proposed formation of an mtDNA deletion through a slipped-strand model of replication.
Figure 3
Figure 4: A simplified diagram of our proposed model for the generation of mtDNA deletions during repair of DSBs.
Figure 5: Proposed model showing how sporadic mtDNA deletions occur in the oocyte.

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Acknowledgements

We wish to acknowledge financial support from the Alzheimer's Research Trust, the Wellcome Trust, EUMitocombat and the Medical Research Council.

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Authors and Affiliations

  1. Kim J. Krishnan, Amy K. Reeve, Patrick F. Chinnery, John K. Blackwood, Robert W. Taylor, Robert N. Lightowlers and Doug M. Turnbull are at the Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. d.m.turnbull@ncl.ac.uk,

    Kim J Krishnan, Amy K Reeve, Patrick F Chinnery, John K Blackwood, Robert W Taylor, Robert N Lightowlers & Doug M Turnbull

  2. Kim J. Krishnan and Doug M. Turnbull are also at the Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK.,

    Kim J Krishnan & Doug M Turnbull

  3. David C. Samuels is at the Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.,

    David C Samuels

  4. Sjoerd Wanrooij and Johannes N. Spelbrink are at the Institute of Medical Technology and Tampere University Hospital, Tampere 33014, Finland.,

    Sjoerd Wanrooij & Johannes N Spelbrink

  5. Department of Metabolic Disease Novum, Sjoerd Wanrooj is also at the Karolinska Institute, SE-141 86, Huddinge, Sweden.,

    Sjoerd Wanrooij

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Krishnan, K., Reeve, A., Samuels, D. et al. What causes mitochondrial DNA deletions in human cells?. Nat Genet 40, 275–279 (2008). https://doi.org/10.1038/ng.f.94

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