Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson's disease.
Following the discovery of inhibition of electron transport complex 1 by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a parkinsonian syndrome in humans, monkeys, and mice, several laboratories have reported abnormalities of complex I and other electron transport complexes (ETCs) in various tissues from patients with Parkinson's disease (PD). Criticism of the significance of these findings in the etiology of PD has centered on whether drug treatments or the debilitation of the disease process itself produced the low ETC activities. We present results from a blinded study of platelet mitochondrial ETC activities in 18 early untreated PD patients and 18 age- and sex-matched controls and in 13 spousal controls. Lower complex I activity in platelet mitochondria of PD patients was seen in early untreated disease and thus cannot be due to debilitation or drug therapy. Home environmental factors seem an unlikely explanation for the reduced complex I activity in PD patients but have not been excluded. Complex II/III activity was also reduced by 20% in PD compared with age-/sex-matched controls. The low complex I and II/III activities in platelet mitochondria appear to be related to the etiology of PD.
Haas
R H
RH
Department of Neurosciences, University of California-San Diego, La Jolla 92093-0935, USA.
Nasirian
F
F
Nakano
K
K
Ward
D
D
Pay
M
M
Hill
R
R
Shults
C W
CW
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000201:enzymology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology*; D012907:Smoking; D013385:Succinate Dehydrogenase / Q000378:metabolism*
D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D002950:Citrate (si)-Synthase; D014450:Electron Transport Complex III