Fyn kinase regulates translation in mammalian mitochondria.
Fyn kinase regulates translation in mammalian mitochondria.
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Fyn 激酶调节哺乳动物线粒体的翻译。
DOI：
10.1016/j.bbagen.2016.12.004
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Koc,Hasan
中科院分区：
文献类型：
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作者：
Koc,EmineC;Miller-Lee,JenniferL;Koc,Hasan
背景哺乳动物线粒体的翻译机制主要是合成氧化磷酸化复合物（oxidizationphosphorylation complex，OXPHOS）的13个亚基。因此，它在线粒体能量产生中起着关键作用。然而，线粒体翻译机制的调控仍然知之甚少。在对正常和病变组织和细胞系的全面蛋白质组学研究中，我们和其他人发现大多数线粒体核糖体蛋白（MRP）被磷酸化。无论是这些磷酸化事件的激酶，也不是他们的具体角色在线粒体translation.MethodsMitochondrial激酶负责磷酸化的MRPs丰富的牛线粒体通过强阳离子交换色谱和基于质谱的蛋白质组学分析的激酶丰富的馏分。重组MRP和55S核糖体的磷酸化通过使用富含激酶的组分的体外磷酸化测定来评估。通过各种细胞生物学和免疫印迹approaches.ResultsHere，我们提供了第一个证据的关联Fyn激酶，Src家族激酶，与线粒体翻译组件和其参与磷酸化的55S核糖体蛋白体外激酶的激酶对OXPHOS和线粒体翻译的影响进行了评估。在人类细胞系中Fyn表达的调节提供了线粒体翻译和能量代谢之间的联系，这是显而易见的变化，在13个natrially编码的亚基的OXPHOS complexes.Conclusions和一般意义我们的研究结果表明，Fyn激酶是一个复杂的机制，可能是通过酪氨酸磷酸化的翻译组件在哺乳动物线粒体中调节蛋白质合成和OXPHOS的一部分。
BackgroundMitochondrial translation machinery solely exists for the synthesis of 13 mitochondrially-encoded subunits of the oxidative phosphorylation (OXPHOS) complexes in mammals. Therefore, it plays a critical role in mitochondrial energy production. However, regulation of the mitochondrial translation machinery is still poorly understood. In comprehensive proteomics studies with normal and diseased tissues and cell lines, we and others have found the majority of mitochondrial ribosomal proteins (MRPs) to be phosphorylated. Neither the kinases for these phosphorylation events nor their specific roles in mitochondrial translation are known.MethodsMitochondrial kinases are responsible for phosphorylation of MRPs enriched from bovine mitoplasts by strong cation-exchange chromatography and identified by mass spectrometry-based proteomics analyses of kinase rich fractions. Phosphorylation of recombinant MRPs and 55S ribosomes was assessed byin vitrophosphorylation assays using the kinase-rich fractions. The effect of identified kinase on OXPHOS and mitochondrial translation was assessed by various cell biological and immunoblotting approaches.ResultsHere, we provide the first evidence for the association of Fyn kinase, a Src family kinase, with mitochondrial translation components and its involvement in phosphorylation of 55S ribosomal proteinsin vitro. Modulation of Fyn expression in human cell lines has provided a link between mitochondrial translation and energy metabolism, which was evident by the changes in 13 mitochondrially encoded subunits of OXPHOS complexes.Conclusions and general significanceOur findings suggest that Fyn kinase is part of a complex mechanism that regulates protein synthesis and OXPHOS possibly by tyrosine phosphorylation of translation components in mammalian mitochondria.