Aim: 

Oxidative stress and mitochondrial dysfunction, especially at the level of complex I of the electronic transport chain, have been proposed to be involved in the pathogenesis of Parkinson's Disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species (DAQs). It has been shown that DA oxidation products, including DAQs, can induce various forms of mitochondrial dysfunction, such as mitochondrial swelling and decreased electron transport chain activity.

Methods: 

In the present work, we focused our attention on the potentially toxic effects of DAQs on mitochondria and, specifically, on the NADH and GSH pool consumption.

Results: 

Our results demonstrate that the generation of DAQs in isolated respiring mitochondria induces the oxidation of NADH. We then characterized in vitro, by UV and NMR spectroscopy, the reactivity of different DA-derived quinones, i.e., dopamine-o-quinone (DQ), aminochrome (AC) and indole-quinone (IQ), toward NADH. We also considered the protective role exerted by GSH.

Conclusion: 

Our results indicate a very diverse reactivity for the different DAQs studied that may contribute to unravel the complex molecular mechanisms underlying oxidative stress and mitochondria dysfunction in the context of PD.