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.

线粒体在必需的细胞功能中起关键作用，例如能量产生，代谢途径和衰老。生长因子介导的线粒体氧化磷酸化（OXPHOS）复合蛋白的表达在代谢稳态中起着基本作用。尽管蛋白质翻译受到一般RNA结合蛋白的影响，但对线粒体oxphos蛋白翻译所涉及的机制知之甚少。在本研究中，血清刺激诱导了核编码的OXPHOS蛋白表达，例如NDUFA9，NDUFB8，SDHB和UQCRFS1和线粒体ATP的产生，以翻译依赖性的方式产生。我们还观察到，主要的mRNA核糖核蛋白Y-盒结合蛋白-1（YB-1）优先与这些Oxphos mRNA结合，并调节从无活性的允许信使核糖核蛋白颗粒（mRNPS）募集mRNA到活性多粒细胞。 YB-1耗竭导致通过MRNP释放的Oxphos蛋白翻译诱导线粒体功能上调。相比之下，YB-1的过表达通过减少多聚体组的形成抑制了这些Oxphos mRNA的翻译，这表明YB-1通过mRNA结合调节了线粒体oxphos mRNA的翻译。综上所述，我们的发现表明YB-1是可以控制OXPHOS活性的翻译的关键因素。