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

Bender, Andreas; Krishnan, Kim J; Morris, Christopher M; Taylor, Geoffrey A; Reeve, Amy K; Perry, Robert H; Jaros, Evelyn; Hersheson, Joshua S; Betts, Joanne; Klopstock, Thomas; Taylor, Robert W; Turnbull, Douglass M

doi:10.1038/ng1769

Cited by 1,570Mitochondrial Function and PathologyParkinson's Disease Mechanisms and TreatmentsAutophagy in Disease and Therapy

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

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Bender, Andreas, Krishnan, Kim J, Morris, Christopher M, Taylor, Geoffrey A, Reeve, Amy K, Perry, Robert H, Jaros, Evelyn, Hersheson, Joshua S +4 more·2006·Nature Genetics

DOI 10.1038/ng1769

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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.

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Aberrant mitochondrial functioning has been implicated in the pathogenesis of idiopathic PD with genetic analysis focusing on age-related mtDNA mutations.
“Aberrant mitochondrial functioning has been implicated in the pathogenesis of idiopathic PD with genetic analysis focusing on age-related mtDNA mutations (Bender et al., 2006; Coxhead et al., 2015; Hudson et al., 2014; Keogh and Chinnery, 2015; Kraytsberg et al., 2006).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Bender et al., 2006
Midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function.
“It has recently been demonstrated that midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function.”
From Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons (2007) · cites this paper as [7]

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Authors: Bender, A., Krishnan, K. J., Morris, C. M., Taylor, G. A., Reeve, A. K., Perry, R. H., Jaros, E., Hersheson, J. S., Betts, J., Klopstock, T., Taylor, R. W., & Turnbull, D. M.
Affiliations: Newcastle University (GB)
Newcastle upon Tyne Hospital (GB)
Ludwig-Maximilians-Universität München (DE)
Corresponding author: Turnbull, Douglass M
ORCID: Bender, Andreas
Morris, Christopher M
Reeve, Amy K
Klopstock, Thomas
Taylor, Robert W
Turnbull, Douglass M
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2006-04-09
Volume: 38
Issue: 5
Pages: 515-517
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng1769
OpenAlex: W2033832481
Cited by: 1,570
References: 15
Citations by year: 2026: 46 · 2025: 55 · 2024: 62 · 2023: 68 · 2022: 96 · 2021: 84 · 2020: 98 · 2019: 81 · 2018: 79 · 2017: 73 · 2016: 82 · 2015: 85 · 2014: 76 · 2013: 72 · 2012: 83
FWCI: 32.39
Type: journal article
Language: en
Open access: green
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
OPUS (Augsburg University) (submittedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: Wellcome Trust (074454)
Medical Research Council (G0700718)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords: mitochondrial DNA deletions, Parkinson's disease, substantia nigra neurons, brain aging, somatic mtDNA mutations, clonal expansion, respiratory chain deficiency, selective neuronal loss, mitochondrial dysfunction
MeSH terms: Aging, Base Sequence, DNA, Mitochondrial, Humans, Parkinson Disease, Substantia Nigra, Sequence Deletion

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

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