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Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease
Author(s) -
Gu M.,
Cooper J. M.,
Taanman J. W.,
Schapira A. H. V.
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440207
Subject(s) - mitochondrial dna , cytochrome c oxidase , mitochondrion , biology , mitochondrial respiratory chain , parkinson's disease , respiratory chain , mutation , human mitochondrial genetics , genetics , coenzyme q – cytochrome c reductase , microbiology and biotechnology , disease , cytochrome c , gene , pathology , medicine
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 (μ o ) 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 μ O /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 μ o 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.