High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease.
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.
Bender
Andreas
A
Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK.
Krishnan
Kim J
KJ
Morris
Christopher M
CM
Taylor
Geoffrey A
GA
Reeve
Amy K
AK
Perry
Robert H
RH
Jaros
Evelyn
E
Hersheson
Joshua S
JS
Betts
Joanne
J
Klopstock
Thomas
T
Taylor
Robert W
RW
Turnbull
Douglass M
DM
D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D017384:Sequence Deletion; D013378:Substantia Nigra / Q000473:pathology*
D004272:DNA, Mitochondrial