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Molecular Mechanism of co-ordinately translational regulation between outer and inner mitochondria

线粒体内外协调翻译调控的分子机制

基本信息

批准号：
21590337
负责人：
UCHIUMI Takeshi
金额：
$ 3万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590337/
关键词：
ミトコンドリア翻訳酸化的リン酸化 YB-1

项目摘要

Mitochondria play key roles in essential cellular functions such as energy production, metabolic pathways and aging. Growth factor-mediated expression of the mitochondrial oxidative phosphorylation(OXPHOS) complex proteins has been proposed to play a fundamental role in metabolic homeostasis. Although protein translation is affected by general RNA-binding proteins, very little is known about the mechanism involved in mitochondrial OXPHOS protein translation. In the present study, serum stimulation induced the nuclear-encoded OXPHOS protein expression such as NDUFA9, NDUFB8, SDHB and UQCRFS1 and mitochondrial ATP production in translation-dependent manners. We also observed that the major mRNA ribonucleoprotein Y-box binding protein-1(YB-1) preferentially bound to these OXPHOS mRNA and regulated the recruitment of mRNAs from inactive messenger ribonucleoprotein particles(mRNPs) to active polysomes. YB-1 depletion led to upregulation of mitochondrial function through induction of OXPHOS protein translation from mRNP release. In contrast, YB-1 overexpression suppressed the translation of these OXPHOS mRNAs through reduced polysome formation, suggesting that YB-1 regulated the translation of mitochondrial OXPHOS mRNAs through mRNA binding. Taken together, our findings suggest that YB-1 is a critical factor for translation that may control OXPHOS activity.

线粒体在能量产生、代谢途径和衰老等基本细胞功能中发挥着关键作用。生长因子介导的线粒体氧化磷酸化（OXPHOS）复合蛋白的表达已被认为在代谢稳态中发挥重要作用。尽管蛋白质翻译受到一般 RNA 结合蛋白的影响，但人们对线粒体 OXPHOS 蛋白质翻译所涉及的机制知之甚少。在本研究中，血清刺激诱导核编码的 OXPHOS 蛋白表达，如 NDUFA9、NDUFB8、SDHB 和 UQCRFS1，以及以翻译依赖性方式产生线粒体 ATP。我们还观察到主要 mRNA 核糖核蛋白 Y-box 结合蛋白-1 (YB-1) 优先与这些 OXPHOS mRNA 结合，并调节 mRNA 从非活性信使核糖核蛋白颗粒 (mRNP) 招募到活性多聚核糖体。 YB-1 耗竭通过诱导 mRNP 释放中的 OXPHOS 蛋白翻译而导致线粒体功能上调。相反，YB-1 过表达通过减少多核糖体形成抑制这些 OXPHOS mRNA 的翻译，表明 YB-1 通过 mRNA 结合调节线粒体 OXPHOS mRNA 的翻译。综上所述，我们的研究结果表明，YB-1 是可能控制 OXPHOS 活性的翻译关键因子。