Re-evaluation of the dysfunction of mitochondrial respiratory chain in skeletal muscle of patients with Parkinson's disease.
The origin and tissue distribution of the mitochondrial dysfunction in Parkinson's disease (PD) remains still a matter of controversy. To re-evaluate a probably free radical-born, generalized mitochondrial impairment in PD, we applied optimized enzymatic assays, high resolution oxygraphic measurements of permeabilized muscle fibers, and application of metabolic control analysis to skeletal muscle samples of 19 PD patients and 36 age-matched controls. We detected decreased activities of respiratory chain complexes I and IV being accompanied by increased flux control coefficients of complexes I and IV on oxygen consumption of muscle fibers. We further investigated if randomly distributed point mutations in two discrete regions of the mitochondrial DNA are increased in PD muscle, and if they could contribute to the mitochondrial impairment. Our data confirm the previously debated presence of a mild mitochondrial defect in skeletal muscle of patients with PD which is accompanied with an about 1.5 to 2-fold increase of point mutated mtDNA.
Winkler-Stuck
K
K
Klinik für Neurologie, Otto-von-Guericke-Universität, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
Kirches
E
E
Mawrin
C
C
Dietzmann
K
K
Lins
H
H
Wallesch
C-W
CW
Kunz
W S
WS
Wiedemann
F R
FR
D000328:Adult; D000368:Aged; D019069:Cell Respiration / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport / Q000235:genetics*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics
D004272:DNA, Mitochondrial; D005609:Free Radicals