The preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta is responsible for the motor impairment associated with Parkinson's disease. Dopamine is a highly reactive molecule, which is usually stored inside synaptic vesicles where it is stabilized by the ambient low pH. However, free cytosolic dopamine can auto-oxidize, generating reactive oxygen species, and lead to the formation of toxic quinones. In the present work, we have analyzed the mechanisms through which the dysfunction of dopamine homeostasis could induce cell toxicity, by focusing in particular on the damage induced by dopamine oxidation products at the mitochondrial level. Our results indicate that dopamine derivatives affect mitochondrial morphology and induce mitochondrial membrane depolarization, leading to a reduction of ATP synthesis. Moreover, our results suggest that opening of the mitochondrial transition pore induced by dopamine-derived quinones may contribute to the specific Parkinson's disease-associated vulnerability of dopamine containing neurons.

中文翻译：

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多巴胺氧化产物作为线粒体内毒素，是帕金森氏病优先神经变性的潜在分子机制。

黑质致密部中多巴胺能神经元的优先变性是造成与帕金森氏病相关的运动障碍的原因。多巴胺是一种高反应性分子，通常存储在突触小泡中，并通过周围的低pH值使其稳定。但是，游离的胞质多巴胺会自动氧化，产生活性氧，并导致有毒醌的形成。在目前的工作中，我们特别关注了线粒体水平上多巴胺氧化产物引起的损伤，从而分析了多巴胺稳态失调可诱导细胞毒性的机制。我们的结果表明，多巴胺衍生物会影响线粒体形态并诱导线粒体膜去极化，从而导致ATP合成减少。