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Journal ArticleDOI

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

TLDR
It is shown that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA, suggesting that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.
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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Citations
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Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

TL;DR: Treatments targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria hold great promise in ageing-related neurodegenerative diseases.
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Mechanisms of mitophagy

TL;DR: Mitophagy, the specific autophagic elimination of mitochondria, has been identified in yeast, and in mammals during red blood cell differentiation, mediated by NIP3-like protein X (NIX; also known as BNIP3L).
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PINK1 is selectively stabilized on impaired mitochondria to activate Parkin.

TL;DR: The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.
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Mitochondria: In Sickness and in Health

TL;DR: This work provides a current view of how mitochondrial functions impinge on health and disease and identifies mitochondrial dysfunction as a key factor in a myriad of diseases, including neurodegenerative and metabolic disorders.
Journal ArticleDOI

Mitochondria: Dynamic Organelles in Disease, Aging, and Development

TL;DR: Recent work is discussed that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease.
References
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Journal ArticleDOI

Ageing and parkinson's disease: substantia nigra regional selectivity

Julian Fearnley, +1 more
- 01 Oct 1991 - 
TL;DR: It is suggested that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of Parkinson's disease and the regional selectivity of PD is relatively specific.
Journal ArticleDOI

Premature ageing in mice expressing defective mitochondrial DNA polymerase

TL;DR: The results provide a causative link between mtDNA mutations and ageing phenotypes in mammals by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase.
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Mitochondrial dna mutations in human disease

TL;DR: This review explores the advances that have been made and the areas in which future progress is likely in understanding basic mitochondrial genetics and the relationship between inherited mutations and disease phenotypes, and in identifying acquired mtDNA mutations in both ageing and cancer.
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Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons

TL;DR: Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA molecules with deletions, it is shown that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions.
Journal ArticleDOI

Detection of a specific mitochondrial DNA deletion in tissues of older humans

TL;DR: Using PCR, it is found that normal heart muscle and brain from adult human individuals contain low levels of a specific mitochondrial DNA deletion, previously found only in patients affected with certain types of neuromuscular disease.
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