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.
University Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, UK.
M
M
Gu
J M
JM
Cooper
J W
JW
Taanman
A H
AH
Schapira
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