The influence of environmental insults on the onset and progression of mitochondrial diseases is unknown. To evaluate the effects of infection on mitochondrial disease we used a mouse model of Leigh Syndrome, where a missense mutation in the Taco1 gene results in the loss of the translation activator of cytochrome c oxidase subunit I (TACO1) protein. The mutation leads to an isolated complex IV deficiency that mimics the disease pathology observed in human patients with TACO1 mutations. We infected Taco1 mutant and wild-type mice with a murine cytomegalovirus and show that a common viral infection exacerbates the complex IV deficiency in a tissue-specific manner. We identified changes in neuromuscular morphology and tissue-specific regulation of the mammalian target of rapamycin pathway in response to viral infection. Taken together, we report for the first time that a common stress condition, such as viral infection, can exacerbate mitochondrial dysfunction in a genetic model of mitochondrial disease.

环境污染对线粒体疾病发作和发展的影响尚不清楚。为了评估感染对线粒体疾病的影响，我们使用了利氏综合征的小鼠模型，其中Taco1基因的错义突变导致细胞色素C氧化酶亚基I（TACO1）蛋白的翻译激活因子的丢失。该突变导致孤立的复杂IV缺乏症，其模仿了在具有TACO1突变的人类患者中观察到的疾病病理。我们感染了Taco1鼠巨细胞病毒的突变和野生型小鼠，并显示常见的病毒感染以组织特异性方式加剧了复杂的IV缺乏症。我们确定了对病毒感染的雷帕霉素途径的哺乳动物靶标的神经肌肉形态和组织特异性调节的变化。综上所述，我们首次报道常见的应激条件，例如病毒感染，可加剧线粒体疾病遗传模型中的线粒体功能障碍。