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

Andreas Bender^1, 4, 5, Kim J Krishnan^1, 5, Christopher M Morris², Geoffrey A Taylor¹, Amy K Reeve¹, Robert H Perry³, Evelyn Jaros³, Joshua S Hersheson¹, Joanne Betts¹, Thomas Klopstock⁴, Robert W Taylor¹ & Douglass M Turnbull¹

¹  Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK.

²  MRC Building, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK.

³  Department of Neuropathology, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK.

⁴  Department of Neurology, University of Munich, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.

⁵  These authors contributed equally to this work.

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.

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