Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease

Abstract

Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% ± 9.3%; individuals with Parkinson disease, 52.3% ± 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Respiratory chain deficiency and analysis of mtDNA deletions in substantia nigra neurons.
Figure 2: Characterization and quantification of mtDNA deletion in substantia nigra neurons from individuals with Parkinson disease and from age-matched controls.

Similar content being viewed by others

References

  1. Taylor, R.W. & Turnbull, D.M. Nat. Rev. Genet. 6, 389–402 (2005).

    Article  CAS  Google Scholar 

  2. Johnson, M.A., Turnbull, D.M., Dick, D.J. & Sherratt, H.S. J. Neurol. Sci. 60, 31–53 (1983).

    Article  CAS  Google Scholar 

  3. Sciacco, M., Bonilla, E., Schon, E.A., DiMauro, S. & Moraes, C.T. Hum. Mol. Genet. 3, 13–19 (1994).

    Article  CAS  Google Scholar 

  4. Cortopassi, G.A. & Arnheim, N. Nucleic Acids Res. 18, 6927–6933 (1990).

    Article  CAS  Google Scholar 

  5. Müller-Höcker, J. Am. J. Pathol. 134, 1167–1173 (1989).

    PubMed  PubMed Central  Google Scholar 

  6. Taylor, R.W. et al. J. Clin. Invest. 112, 1351–1360 (2003).

    Article  CAS  Google Scholar 

  7. Fearnley, J.M. & Lees, A.J. Brain 114, 2283–2301 (1991).

    Article  Google Scholar 

  8. Greene, J.G., Dingledine, R. & Greenamyre, J.T. Neurobiol. Dis. 18, 19–31 (2005).

    Article  CAS  Google Scholar 

  9. Smeyne, R.J. & Jackson-Lewis, V. Brain Res. Mol. Brain Res. 134, 57–66 (2005).

    Article  CAS  Google Scholar 

  10. Itoh, K., Weis, S., Mehraein, P. & Muller-Hocker, J. Neurobiol. Aging 17, 843–848 (1996).

    Article  CAS  Google Scholar 

  11. Cottrell, D.A. et al. Neurobiol. Aging 22, 265–272 (2001).

    Article  CAS  Google Scholar 

  12. He, L. et al. Nucleic Acids Res. 30, e68 (2002).

    Article  Google Scholar 

  13. Trifunovic, A. et al. Nature 429, 417–423 (2004).

    Article  CAS  Google Scholar 

  14. Kraytsberg, Y. et al. Nat. Genet., advance online publication 2 April 2006 (doi: 10.1038/ng1778).

  15. Luoma, P. et al. Lancet 364, 875–882 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work has been supported by Alzheimer's Research Trust, Wellcome Trust, Medical Research Council UK and European Neurological Society.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Douglass M Turnbull.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Characterization of real-time PCR assay. (PDF 54 kb)

Supplementary Table

Primers used. (PDF 73 kb)

Supplementary Methods (PDF 108 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bender, A., Krishnan, K., Morris, C. et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38, 515–517 (2006). https://doi.org/10.1038/ng1769

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1769

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing