title: 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 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.
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coxhead
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK.
authors.forename: Marzena
authors.initials: M
authors.lastname: Kurzawa-Akanbi
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK.
authors.forename: Rafiqul
authors.initials: R
authors.lastname: Hussain
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chinnery
authors.affiliation: Mitochondrial Research Group, Institute of Genetic Medicine, University of Newcastle Upon Tyne, UK. Electronic address: Gavin.Hudson@ncl.ac.uk.
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
mesh_terms: D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV
keywords: Mitochondria; Neurodegeneration; Parkinson's disease; Somatic mutation