MITOCHONDRIAL-DNA TRANSMISSION OF THE MITOCHONDRIAL DEFECT IN PARKINSONS-DISEASE

Several groups have identified mitochondrial complex I deficiency in P arkinson's disease (PD) substantia nigra and in platelets. A search fo r any mitochondrial DNA (mtDNA) mutation underlying this defect has no t yet produced any consistent result. We have made use of a mtDNA-less (rho(0)) cell line to determine if the complex I deficiency follows t he 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 ana lysis and demonstrated a selective 25% deficiency of complex I activit y. Individual clonal analysis of A549 rho(0)/PD platelet fusion cybrid s from 1 of the patients expressed combined complex I and IV deficienc ies with 25% and 20% decreased activities in the PD clones, respective ly. Histocytochemical, immunocytochemical, and cellular functional ima ging studies of these clones showed the cells within the clones were h eterogeneous 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 th at an mtDNA abnormality may underlie the mitochondrial defect in at le ast a proportion of PD patients. This rho(0) 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.