Novel mitochondrial DNA mutations in Parkinson's disease

Summary. Despite the recent discovery of several chromosomal gene mutations in familial Parkinson's disease (PD) the genetic background for idiopathic PD remains to be elusive. Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) action on dopaminergic neuronal cells and the specific decrease of mitochondrial complex I activity in substantia nigra of PD patients mitochondrial biochemistry and genetics emerged to become Pandora's box in the pathogenesis of PD. One approach was to establish the potential role of defective mitochondrial DNA (mtDNA). As complex I genes are the most vulnerable part of mtDNA we analyzed the mitochondrial MTND1 and MTND2 genes of 10 substantia nigra and 85 platelet samples from PD patients. We were uneventful to detect heteroplasmic base changes even applying techniques able to visualize mutations with low percentage of heteroplasmy but here we report novel homoplasmic base changes. These results add further evidence that there are no inherited disease specific mtDNA mutations, hence individual homoplasmic mutations or very low grade heteroplasmic mutations in the vicinity of mitochondrial metabolism and oxidative stress may contribute to selective neuronal vulnerability in PD. Received February 4, 2002; accepted February 27, 2002