Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease.

Abstract

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.

• Authors: M Gu, J M Cooper, J W Taanman, A H Schapira
• Journal: Annals of neurology (Ann Neurol) Vol. 44 Issue 2 Pg. 177-86 (Aug 1998) ISSN: 0364-5134 [Print] United States
• PMID: 9708539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Carbocyanines
• DNA, Mitochondrial
• Fluorescent Dyes
• Platelet Membrane Glycoproteins
• 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine

Topics

• Benzimidazoles (analysis)
• Blood Platelets (metabolism)
• Carbocyanines (analysis)
• Clone Cells (metabolism)
• DNA, Mitochondrial (genetics)
• Electron Transport
• Fluorescent Dyes (analysis)
• Humans
• Immunohistochemistry
• Mitochondria (genetics, metabolism)
• Mutation
• Parkinson Disease (genetics)
• Platelet Membrane Glycoproteins (metabolism)
• Polymerase Chain Reaction