title: Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons.
abstract: Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA (mtDNA) molecules with deletions, we show that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions. Molecules with deletions are largely clonal within each neuron; that is, they originate from a single deleted mtDNA molecule that has expanded clonally. The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Yevgenya
authors.initials: Y
authors.lastname: Kraytsberg
authors.forename: Elena
authors.initials: E
authors.lastname: Kudryavtseva
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.forename: Changiz
authors.initials: C
authors.lastname: Geula
authors.forename: Neil W
authors.initials: NW
authors.lastname: Kowall
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khrapko
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV