Function of mitochondrial complex-I and -IV in normal human and Parkinson's disease cybrids



Mitochondrial dysfunction has been implicated in the dopaminergic neurodegeneration, which characterizes Parkinson’s disease (PD). The activities of mitochondrial complexes I and IV were found to be reduced in the brains of PD patients (n = 4) as compared to age-matched controls (n = 4). This is tested in SH-SY5Y cell lines, transformed Rho0 cells, and in normal and PD cybrid cell lines. Cybrids were created by fusion of the Rho0 cells with platelets from PD patients and age-matched normal humans. The reduction in activities was found to be stably transferred to PD cybrids. By Western blotting, it was found that the expression of the subunits of the two complexes was also aberrant in the patient brain samples. Most of the PD cybrids showed a decreased expression of the subunits of complexes I and IV. While administration of coenzyme Q10 was found to increase complex I activity in the control cybrids, no such recovery was found in the PD cybrids. These results indicate decline of both complex-I and -IV activities and their subunits expression in most cases of sporadic PD. Cybrids could be a useful tool for investigating mitochondrial gene abnormalities in PD. While coenzyme Q10 was effective in cybrids from the aged, it was found to be ineffective in sporadic PD. These results suggest an active involvement of the components of the electron transport chain in PD, and offer scope for meaningful investigation into neuroprotective strategies relevant to humans.