RESPIRATORY-CHAIN AND MITOCHONDRIAL-DNA IN MUSCLE AND BRAIN IN PARKINSONS-DISEASE PATIENTS

There are several reports of a defect of complex I in the substantia n igra (SN) of Parkinson's disease (PD) patients. To evaluate whether th is is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative pho sphorylation (OXPHOS) system, we measured respiratory enzyme activitie s in muscle homogenates from 16 PD patients and eight age-matched cont rols, and in muscle isolated mitochondria of six PD patients and six a ge-matched controls. We found no difference between the PD and control groups. In addition, we detected, by polymerase chain reaction, the m itochondrial DNA (mtDNA) ''common deletion'' (CD) in muscle specimens of 14 of 17 PD patients, but we obtained similar results in age-matche d controls. In both groups, the amount of CD-specific deleted (DELTA) mtDNA ranged from 0.0% to 0.1%. Our data suggest that PD cannot be att ributed to a multisystem decline of mitochondrial OXPHOS, and that les ions of muscle mtDNA in PD are likely due to normal aging. However, th ere was a remarkable accumulation of DELTAmtDNA in the SN of a PD pati ent and an age-matched control, suggesting that the SN is exquisitely sensitive to age-dependent damage of the mitochondrial genome.