Aim: 

Mitochondrial dysfunctions, at the level of complex I of the electronic transport chain (ETC), have been reported in the SNpc of Parkinson Disease (PD) patients. Deficits in complex I observed in PD patients are indicative of a bioenergetic defect and increased reactive oxygen species (ROS) production due to electron leak from ETC. Consistent with this, lipid peroxidation and protein carbonyls are present in striatum of post-mortem PD brains, indicative of exposure to ROS. Additionally, a specific decrease in the anti-oxidant glutathione (GSH) has been reported in the SNpc of PD patients, suggesting that these neurons may not be able to buffer the ROS. The working hypothesis that is evaluated, previously proposed in the literature, is that the oxidized products of the neurotransmitter Dopamine (DAQs) may induce toxic effects on mitochondria. The mechanism of the proposed toxicity will be considered in relation to the several steps that starting from the oxidation of dopamine in the medium lead to the modification of the protein targets in the mitochondria.

Results: 

This research demonstrates that the oxidized products of dopamine but not dopamine itself can enter the mitochondria. The DAQs react to covalently modify more then one proteins target within mitochondria. Several potential functional consequences of DAQs action on mitochondria were evaluated in isolated mitochondria and in cells.

Conclusion: 

mitochondrial dysfunctions derived from exposure to DA-oxidized products could account for the specific vulnerability of dopaminergic neurons and their degeneration in PD.