Journal ArticleDOI
High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease.
Andreas Bender,Kim J. Krishnan,Christopher Morris,Geoffrey A. Taylor,Amy K. Reeve,Robert H. Perry,Evelyn Jaros,Joshua S Hersheson,Joanne Betts,Thomas Klopstock,Robert W. Taylor,Douglass M. Turnbull +11 more
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.read more
Citations
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Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases
Michael T. Lin,M. Flint Beal +1 more
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.
Journal ArticleDOI
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).
Journal ArticleDOI
PINK1 is selectively stabilized on impaired mitochondria to activate Parkin.
Derek P. Narendra,Seok Min Jin,Atsushi Tanaka,Der-Fen Suen,Clement A. Gautier,Jie Shen,Mark R. Cookson,Richard J. Youle +7 more
TL;DR: The authors suggest that PINK1 and Parkin form a pathway that senses damaged mitochondria and selectively targets them for degradation.
Journal ArticleDOI
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,Andrew J. Lees +1 more
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
Aleksandra Trifunovic,Anna Wredenberg,Maria Falkenberg,Johannes N. Spelbrink,Anja T. Rovio,Carl E.G. Bruder,Mohammad Bohlooly-Y,Sebastian Gidlöf,Anders Oldfors,Rolf Wibom,Jan Törnell,Howard T. Jacobs,Nils-Göran Larsson +12 more
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.
Journal ArticleDOI
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.
Journal ArticleDOI
Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons
Yevgenya Kraytsberg,Elena Kudryavtseva,Ann C. McKee,Ann C. McKee,Changiz Geula,Neil W. Kowall,Neil W. Kowall,Konstantin Khrapko +7 more
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
Gino A Cortopassi,Norman Arnheim +1 more
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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