Mitochondrial oxidative phosphorylation defects in Parkinson's disease.
Parkinson's disease has been associated with defects in oxidative phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays were compared to the 5 to 95% confidence intervals from 16 control subjects. Four patients had complex I defects, whereas 1 patient had a complex IV defect. A genetic basis for Parkinson's disease was suggested by the presence of affected relatives of 2 patients with Parkinson's disease. Known pathological mitochondrial DNA mutations (insertion-deletions or point mutations) were not found. We conclude that Parkinson's disease is a systemic disorder of Oxphos, probably of a complex genetic etiology. Premature cell death in the nigrostriatal dopamine pathway could be due to energetic impairment and accentuated free radical generation caused by an Oxphos defect.
Shoffner
J M
JM
Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322.
Watts
R L
RL
Juncos
J L
JL
Torroni
A
A
Wallace
D C
DC
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D001706:Biopsy; D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis; D005260:Female; D006003:Glycogen / Q000032:analysis; D006801:Humans; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic
D004272:DNA, Mitochondrial; D008055:Lipids; D006003:Glycogen