Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson’s disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron–sulfur containing protein that regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP. Gait analysis revealed a shortened stride length and decreased rotarod performance in knockout mice, consistent with the loss of striatal dopamine. Together, these data suggest that mitoNEET KO mice exhibit many of the characteristics of early neurodegeneration in PD and may provide a novel drug discovery platform to evaluate compounds for enhancing mitochondrial function in neurodegenerative disorders.

中文翻译：

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MitoNEET（CISD1）敲除小鼠显示出纹状体线粒体功能障碍和帕金森氏病表型的迹象

人们认为线粒体功能障碍在帕金森氏病（PD）中观察到的神经退行性变中起重要作用，但尚不清楚这种病理的潜在机制。在这里，我们证明了mitoNEET（CISD1）（一种含铁硫的蛋白质，调节线粒体生物能）的损失会导致线粒体功能障碍以及纹状体多巴胺和酪氨酸羟化酶的损失。从缺乏mitoNEET的小鼠中分离出的线粒体功能失调，表现为活性氧含量（ROS）升高和产生ATP的能力降低。步态分析显示，基因敲除小鼠的步幅缩短，轮转表现降低，这与纹状体多巴胺的丢失是一致的。一起，