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

线粒体在基本细胞功能中起关键作用，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）复合物蛋白的表达已被提出在代谢稳态中发挥重要作用。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蛋白的表达，如NDUFA 9，NDUFB 8，SDHB和UQCRFS 1和线粒体ATP的产生以抑制依赖的方式。我们还观察到，主要的mRNA核糖核蛋白Y盒结合蛋白-1（YB-1）优先结合这些OXPHOS mRNA和调节招聘的mRNA从非活性信使核糖核蛋白颗粒（mRNP）的活性多核糖体。YB-1耗竭通过诱导mRNP释放的OXPHOS蛋白翻译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 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.