Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts.
Analysis of the mechanism of radiation-induced upregulation of mitochondrial abundance in mouse fibroblasts.
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DOI：
10.1093/jrr/rrw113
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发表时间：
2017-05-01
影响因子：
2
通讯作者：
Inanami O
中科院分区：
文献类型：
--
作者：
Yamamori T;Sasagawa T;Ichii O;Hiyoshi M;Bo T;Yasui H;Kon Y;Inanami O
线粒体通过多种机制维持细胞的完整性，包括氧化型三磷酸腺苷的产生和钙稳态的调节。因此，适当地调节线粒体的丰度、分布和活性对于维持细胞内环境的稳定至关重要。以往的研究表明，电离辐射(IR)改变了线粒体的功能，提示线粒体可能是IR的重要靶点。虽然据报道，IR影响细胞线粒体的丰度，但其机制在很大程度上仍不清楚。在这项研究中，我们研究了IR如何影响小鼠成纤维细胞中线粒体的丰度。当小鼠NIH/3T3细胞受到X射线照射时，线粒体DNA(MtDNA)和线粒体质量呈时间依赖性增加，表明辐射诱导线粒体丰度上调。同时，我们不仅没有观察到辐射后自噬活性的显著变化，而且IR对细胞色素c氧化酶亚基IV和细胞色素c两种线粒体蛋白的表达以及DNA聚合酶γ组分PolgmRNA的表达几乎没有影响。我们还观察到参与线粒体生物发生的转录因子的表达仅受到IR的轻微影响。这些数据表明，辐射诱导的线粒体丰度上调是一个独立于宏观自噬和线粒体生物发生的事件。此外，我们还发现了IR诱导长期细胞周期停滞和细胞衰老的证据，表明这些事件参与了对线粒体丰度的调节。考虑到线粒体在细胞放射反应中的重要性，我们相信本研究为理解IR对线粒体的影响提供了新的见解。
Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown. In this study, we examined how IR influences mitochondrial abundance in mouse fibroblasts. When mouse NIH/3T3 cells were exposed to X-rays, a time-dependent increase was observed in mitochondrial DNA (mtDNA) and mitochondrial mass, indicating radiation-induced upregulation of mitochondrial abundance. Meanwhile, not only did we not observe a significant change in autophagic activity after irradiation, but in addition, IR hardly influenced the expression of two mitochondrial proteins, cytochrome c oxidase subunit IV and cytochrome c, or the mRNA expression of Polg, a component of DNA polymerase γ. We also observed that the expression of transcription factors involved in mitochondrial biogenesis was only marginally affected by IR. These data imply that radiation-induced upregulation of mitochondrial abundance is an event independent of macroautophagy and mitochondrial biogenesis. Furthermore, we found evidence that IR induced long-term cell cycle arrest and cellular senescence, indicating that these events are involved in regulating mitochondrial abundance. Considering the growing significance of mitochondria in cellular radioresponses, we believe the present study provides novel insights into understanding the effects of IR on mitochondria.