Oxidative stress and subsequent energy crisis have been proposed as th
e cause of nigral neuronal cell death in Parkinson's disease. We have
reported defects in the mitochondrial respiratory chain and increased
amount of deleted mitochondrial genome in the nigrostriatal system of
patients with Parkinson's disease. Deletion in mitochondrial DNA could
be ascribed to somatically acquired premature aging leading to cell d
eath. To elucidate the contribution of maternally transmitted point mu
tations in mitochondrial DNA to the premature DNA damages, we employed
a direct sequencing system and analyzed the total nucleotide sequence
s of mitochondrial DNA in the brains of five patients with idiopathic
Parkinson's disease. There were no predominant point mutations among t
he patients in contrast to some neuromuscular diseases. However, each
patient had several point mutations that would result in a significant
change in the gene products. Some of these mutations may be involved
either in the increased production of oxygen radicals from the mitocho
ndrial respiratory chain or in the increased susceptibility of the res
piratory chain components to oxidative damage. We propose that some of
these mutations can be regarded as one of the risk factors accelerati
ng degeneration of nigrostriatal pathway in Parkinson's disease.