Somatic mtDNA variation is an important component of Parkinson's disease

Abstract There is a growing body of evidence linking mitochondrial dysfunction, mediated either through inherited mitochondrial DNA (mtDNA) variation or mitochondrial proteomic deficit, to Parkinson's disease (PD). Yet, despite this, the role of somatic mtDNA point mutations and specifically po...

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Bibliographic Details
Published in:Neurobiology of aging 2016-02, Vol.38, p.217.e1-217.e6
Main Authors: Coxhead, Jonathan, Kurzawa-Akanbi, Marzena, Hussain, Rafiqul, Pyle, Angela, Chinnery, Patrick, Hudson, Gavin
Format: Article
Language:English
Subjects:
Cohort Studies
DNA, Mitochondrial - genetics
Electron Transport Complex IV - genetics
Genetic Association Studies
Genetic Report Abstract
Humans
Internal Medicine
Mitochondria
Neurodegeneration
Neurology
Parkinson Disease - genetics
Parkinson's disease
Point Mutation - genetics
Somatic mutation
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Summary:Abstract There is a growing body of evidence linking mitochondrial dysfunction, mediated either through inherited mitochondrial DNA (mtDNA) variation or mitochondrial proteomic deficit, to Parkinson's disease (PD). Yet, despite this, the role of somatic mtDNA point mutations and specifically point-mutational burden in PD is poorly understood. Here, we take advantage of recent technical and methodological advances to examine the role of age-related and acquired mtDNA mutation in the largest study of mtDNA in postmortem PD tissue to date. Our data show that PD patients suffer an increase in mtDNA mutational burden in, but no limited to, the substantia nigra pars compacta when compared to matched controls. This mutational burden appears increased in genes encoding cytochrome c oxidase, supportive of previous protein studies of mitochondrial dysfunction in PD. Accepting experimental limitations, our study confirms the important role of age-related mtDNA point mutation in the etiology of PD, moreover, by analyzing 2 distinct brain regions, we are able to show that PD patient brains are more vulnerable to mtDNA mutation overall.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2015.10.036