Nature Genetics
- 38, 518 - 520 (2006)
Published online: 9 April 2006; | doi:10.1038/ng1778
Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neuronsYevgenya Kraytsberg1, Elena Kudryavtseva1, Ann C McKee2, 3, Changiz Geula1, Neil W Kowall2, 3 & Konstantin Khrapko11
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. 2
Boston University School of Medicine, Boston, Massachusetts 02118, USA. 3
Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, USA.
Correspondence should be addressed to Konstantin Khrapko khrapko@hms.harvard.edu 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.
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