Mitochondrial impairment is one of the most important hallmarks of Parkinson's disease (PD) pathogenesis. In this work, we wanted to verify the molecular basis of altered mitochondrial dynamics and disposal in Substantia nigra specimens of sporadic PD patients, by the comparison with two cellular models of PD. Indeed, SH-SY5Y cells were treated with either dopamine or 1-methyl-4-phenylpyridinium (MPP⁺) in order to highlight the effect of altered dopamine homeostasis and of complex I inhibition, respectively. As a result, we found that fusion impairment of the inner mitochondrial membrane is a common feature of both PD human samples and cellular models. However, the effects of dopamine and MPP⁺ treatments resulted to be different in terms of the mitochondrial damage induced. Opposite changes in the levels of two mitochondrial protein markers (voltage-dependent anion channels (VDACs) and cytochrome c oxidase subunit 5β (COX5β)) were observed. In this case, dopamine treatment better recapitulated the molecular picture of patients' samples. Moreover, the accumulation of PTEN-induced putative kinase 1 (PINK1), a mitophagy marker, was not observed in both PD patients samples and cellular models. Eventually, in transmission electron microscopy images, small electron dense deposits were observed in mitochondria of PD subjects, which are uniquely reproduced in dopamine-treated cells. In conclusion, our study suggests that the mitochondrial molecular landscape of Substantia nigra specimens of PD patients can be mirrored by the impaired dopamine homeostasis cellular model, thus supporting the hypothesis that alterations in this process could be a crucial pathogenetic event in PD.

线粒体损伤是帕金森氏病（PD）发病机理的最重要标志之一。在这项工作中，我们希望通过与两种PD细胞模型进行比较，来验证散发性PD患者黑质标本中线粒体动力学变化和处置的分子基础。实际上，用多巴胺或1-甲基-4-苯基吡啶鎓（MPP ⁺）处理过SH-SY5Y细胞，以分别强调改变多巴胺稳态和复合物I抑制的作用。结果，我们发现内线粒体膜的融合损伤是PD人类样品和细胞模型的共同特征。但是，多巴胺和MPP ^+的作用在诱导的线粒体损伤方面，不同的治疗方法有所不同。两种线粒体蛋白质标记物（电压依赖性阴离子通道（VDAC）和细胞色素c观察到氧化酶亚基5β（COX5β）。在这种情况下，多巴胺治疗可以更好地概括患者样品的分子图像。此外，在PD患者样品和细胞模型中均未观察到PTEN诱导的假定激酶1（PINK1）（一种线粒体标记）的积累。最终，在透射电子显微镜图像中，在PD受试者的线粒体中观察到小的电子致密沉积物，其在多巴胺处理的细胞中独特地再现。总之，我们的研究表明，多巴胺稳态细胞模型受损可以反映PD患者黑质标本的线粒体分子景观，从而支持这一过程中的改变可能是PD中关键的致病事件的假说。