Cytoplasmic transfer of platelet mtDNA from elderly patients with Parkinson's disease to mtDNA-less HeLa cells restores complete mitochondrial respiratory function.
For determination of whether platelet mtDNA in patients with Parkinson's disease (PD) possesses some lesions to reduce respiratory enzyme activities, platelet mtDNA was transferred into mtDNA-less (rho0) HeLa cells from aged PD patients and age-matched normal subjects, since their activities were controlled by both mitochondrial and nuclear genomes. The resultant mtDNA-repopulated cybrid clones containing the HeLa nuclear genome as a common background were used for comparison of respiratory enzyme activities. Remarkable variations of the enzyme activities were observed in the cybrid clones, irrespective of whether their mtDNA was transferred from normal subjects or PD patients, and some of them showed 20% reduction of average activities. Thus, the mtDNA mutations responsible for inducing 20% reduction should be polymorphic rather than pathogenic. On the other hand, pathogenic control cybrid clones possessing mtDNA mutations from patients with mitochondrial disorders showed significant and specific decline of respiratory enzyme complex I activity beyond the normal range of the variations. These observations warrant reassessment of the conventional concept that complex I activity in platelets of PD patients is defective due to mtDNA mutations.
Aomi
Y
Y
Institute of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
Chen
C S
CS
Nakada
K
K
Ito
S
S
Isobe
K
K
Murakami
H
H
Kuno
S Y
SY
Tawata
M
M
Matsuoka
R
R
Mizusawa
H
H
Hayashi
J I
JI
D000368:Aged; D000369:Aged, 80 and over; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000235:genetics; D009154:Mutation; D010101:Oxygen Consumption; D010300:Parkinson Disease / Q000235:genetics*; D012016:Reference Values
D003580:Cytochromes; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III