Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA
Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA
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DOI：
10.1042/bj20111728
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发表时间：
2012-04-15
影响因子：
4.1
通讯作者：
Kang, Dongchon
中科院分区：
文献类型：
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作者：
Matsumoto, Shinya;Uchiumi, Takeshi;Kang, Dongchon
线粒体在基本细胞功能中发挥关键作用，如能量产生、代谢途径和衰老。已经提出生长因子介导的线粒体OXPHOS（氧化磷酸化）复合物蛋白的表达在代谢稳态中起基本作用。虽然蛋白质翻译受一般RNA结合蛋白的影响，但对线粒体OXPHOS蛋白翻译的机制知之甚少。在本研究中，血清刺激诱导核编码的OXPHOS蛋白表达，例如NDUFA 9 [NADH脱氢酶（泛醌）1 α亚复合物，9，39 kDa]，NDUFB 8 [NADH脱氢酶（泛醌）1 β亚复合物，8，19 kDa]、SDHB [琥珀酸脱氢酶复合物，亚基B，铁硫（Ip）]和UQCRFS 1（泛喹啉-细胞色素c还原酶，Rieske铁硫多肽1）和线粒体ATP产生，以抑制依赖性方式。我们还观察到，主要的核糖核蛋白YB-1（Y盒结合蛋白-1）优先结合这些OXPHOS mRNA和调节招聘的mRNA从失活的mRNP（信使核糖核蛋白颗粒）的活性多核糖体。YB-1耗竭通过诱导OXPHOS蛋白从失活mRNP释放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是一个关键因素的翻译，可能控制OXPHOS活动。
Mitochondria play key roles in essential cellular functions, such as energy production, metabolic pathways and aging. Growth factor-mediated expression of the mitochondria] OXPHOS (oxidative phosphorylation) 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 nuclear-encoded OXPHOS protein expression, such as NDUFA9 [NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9, 39 kDa], NDUFB8 [NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8, 19 kDa], SDHB [succinate dehydrogenase complex, subunit B, iron sulfur (Ip)] and UQCRFS1 (ubiquinol-cytochrome c reductase, Rieske iron sulfur polypeptide 1), and mitochondrial ATP production, in a translation-dependent manner. We also observed that the major ribonucleoprotein YB-1 (Y-box-binding protein-1) preferentially bound to these OXPHOS mRNAs and regulated the recruitment of mRNAs from inactive mRNPs (messenger ribonucleoprotein particles) to active polysomes. YB-1 depletion led to up-regulation of mitochondrial function through induction of OXPHOS protein translation from inactive 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.