MITOCHONDRIAL RESPIRATORY-FAILURE IN SKELETAL-MUSCLE FROM PATIENTS WITH PARKINSONS-DISEASE AND MULTIPLE SYSTEM ATROPHY

We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Do pa-treated PD patients and 6 de novo patients), 5 patients with multip le system atrophy (MSA) and from 43 age-matched controls in order to d etermine the occurrence of mitochondrial respiratory chain abnormaliti es in parkinsonian syndromes. In our control subjects, we found a sign ificant age-related decrease in the activity of respiratory chain comp lex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in mus cle mitochondria from patients with PD and MSA and a mean remaining ac tivity < 30% of controls was observed. Mean activities of complexes II I (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) wer e also lower in PD patients than controls, but a low activity (remaini ng activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succ inate: ubiquinone reductase) was observed. Our results support the hyp othesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related defici ency. This deficit can be found in de novo PD patients as well as in t reated patients. The observed respiratory enzyme chain deficiency coul d not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters an d enzyme complexes activities.