Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease.
Several groups have identified mitochondrial complex I deficiency in Parkinson's disease (PD) substantia nigra and in platelets. A search for any mitochondrial DNA (mtDNA) mutation underlying this defect has not yet produced any consistent result. We have made use of a mtDNA-less (p0) cell line to determine if the complex I deficiency follows the genomic transplantation of platelet mtDNA. From a preselected group of PD patients with low platelet complex I activity, 7 patients were used for detailed study. All 7 patients were used for mixed cybrid analysis and demonstrated a selective 25% deficiency of complex I activity. Individual clonal analysis of A549 p0/PD platelet fusion cybrids from 1 of the patients expressed combined complex I and IV deficiencies with 25% and 20% decreased activities in the PD clones, respectively. Histocytochemical, immunocytochemical, and cellular functional imaging studies of these clones showed the cells within the clones were heterogeneous with respect to cytochrome c oxidase (COX) function, COX I content, and mitochondrial respiratory chain activity. These results are in agreement with a previous study and support the proposition that an mtDNA abnormality may underlie the mitochondrial defect in at least a proportion of PD patients. This p0 technology may serve as a means to identify the subgroup of PD patients in whom an mtDNA defect may contribute to development of the disease.
Gu
M
M
University Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, UK.
Cooper
J M
JM
Taanman
J W
JW
Schapira
A H
AH
D001562:Benzimidazoles / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism*; D002232:Carbocyanines / Q000032:analysis; D002999:Clone Cells / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction
D001562:Benzimidazoles; D002232:Carbocyanines; D004272:DNA, Mitochondrial; D005456:Fluorescent Dyes; D010980:Platelet Membrane Glycoproteins; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine