Mitochondrial oxidative phosphorylation defects in parkinson's disease

TLDR

Parkinson’s disease has been linked to oxidative phosphorylation defects that may cause energetic failure and increased free radical production leading to premature death of nigrostriatal dopamine neurons. The study isolated mitochondria from muscle biopsies of six Parkinson’s patients and measured Oxphos enzyme activities, comparing the results to 16 control subjects’ 5–95 % confidence intervals. Four patients exhibited complex I deficiencies, one had a complex IV defect, and although no known mtDNA mutations were detected, the presence of affected relatives in two cases suggests a complex genetic etiology, supporting the conclusion that Parkinson’s disease is a systemic Oxphos disorder.

Abstract

Abstract 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.