Biochemical analysis of cybrids expressing mitochondrial DNA from Contursikindred Parkinson's subjects

Complex I activity is reduced in cytoplasmic hybrid (cybrid) cell lines tha t contain mitochondrial DNA (mtDNA) from sporadic Parkinson's disease (PD) patients. This implies that mtDNA aberration occurs in sporadic PD. To asse ss the integrity of mtDNA in autosomal dominant PD arising from mutation of the alpha -synuclein gene, we transferred mitochondrial genes from PD-affe cted members of the Italian-American Contursi kindred to cells previously d epleted of their endogenous mtDNA Unlike cybrid cell lines expressing mtDNA from persons with sporadic or maternally inherited PD, the resultant Contu rsi cybrid lines did not manifest complex I deficiency, indicating that in Contursi PD mtDNA integrity is relatively preserved. Compared to control cy brids, however, Contursi cybrid lines did show some evidence of oxidative s tress. For reasons that are unclear, at least a limited amount of mtDNA dam age may nevertheless develop in PD patients with alpha -synuclein mutation. (C) 2001 Academic Press.