Mitochondrial DNA in focal dystonia: a cybrid analysis.
The cause and pathophysiology of dystonia remain unknown. The recent identification of mitochondrial complex I deficiency in platelets from patients with sporadic focal dystonia suggests that a defect of energy metabolism may be relevant in a proportion of patients. We have addressed the possible contribution of mitochondrial DNA (mtDNA) to the complex I deficiency in dystonia by the use of genome transfer technology. Platelets from patients deficient for complex I were fused with A549 p0 (mtDNA-less) cells to form cybrids comprising the A549 nucleus and dystonia mtDNA. Mixed cybrid cell lines were analyzed for 9 controls and 9 dystonia patients, and clonal cybrid lines were generated for 2 control and 2 dystonia patients. Subsequent biochemical analysis showed that the dystonia complex I defect was complemented in both the mixed and the clonal cybrid lines. These results contrast with similar studies in mitochondrial myopathy and Parkinson's disease patients, in which the mitochondrial defect was maintained in at least a proportion of A549 cybrids, and suggest that the complex I defect in dystonia is not caused by an mtDNA mutation.
Tabrizi
S J
SJ
University Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, UK.
Cooper
J M
JM
Schapira
A H
AH
D001792:Blood Platelets / Q000378:metabolism*; D002459:Cell Fusion; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000032:analysis*; D004421:Dystonia / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D012016:Reference Values; D018709:Statistics, Nonparametric
D004272:DNA, Mitochondrial; D016660:NAD(P)H Dehydrogenase (Quinone); D002950:Citrate (si)-Synthase