Clueless is a conserved ribonucleoprotein that binds the ribosome at the mitochondrial outer membrane
Clueless is a conserved ribonucleoprotein that binds the ribosome at the mitochondrial outer membrane
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DOI：
10.1242/bio.015313
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发表时间：
2016-02-15
期刊：
影响因子：
2.4
通讯作者：
Cox, Rachel T.
中科院分区：
文献类型：
--
作者：
Sen, Aditya;Cox, Rachel T.
线粒体的功能与细胞核紧密相连，因为细胞核基因编码的数百种蛋白质必须输入线粒体。虽然翻译后输入已被充分理解，但新出现的证据支持线粒体位点特异性输入或共翻译输入也会发生。然而，其机制和使用的程度还没有完全了解。我们之前已经证明Clueless （Clu）是一种保守的多结构域蛋白，与线粒体外膜蛋白（包括外膜转位酶20）相关，并与PINK1-Parkin通路进行遗传和物理相互作用。Clu的人类同源基因Cluh被证明可以结合核编码的线粒体mrna。在这里，我们确定了Clu的保守的四肽结构域主要负责结合mRNA。此外，我们发现Clu与线粒体外膜的核糖体相互作用。综上所述，这些数据支持一个模型，即Clu结合线粒体靶向mRNA，促进mRNA定位到线粒体外膜，可能用于位点特异性或共翻译输入。这一作用可能通过PINK1-Parkin通路将有效的线粒体蛋白输入与线粒体质量控制联系起来。
Mitochondrial function is tied to the nucleus, in that hundreds of proteins encoded by nuclear genes must be imported into mitochondria. While post-translational import is fairly well understood, emerging evidence supports that mitochondrial site-specific import, or co-translational import, also occurs. However, the mechanism and the extent to which it is used are not fully understood. We have previously shown Clueless (Clu), a conserved multi-domain protein, associates with mitochondrial outer membrane proteins, including Translocase of outer membrane 20, and genetically and physically interacts with the PINK1-Parkin pathway. The human ortholog of Clu, Cluh, was shown to bind nuclear-encoded mitochondrially destined mRNAs. Here we identify the conserved tetratricopeptide domain of Clu as predominantly responsible for binding mRNA. In addition, we show Clu interacts with the ribosome at the mitochondrial outer membrane. Taken together, these data support a model whereby Clu binds to and mitochondrially targets mRNAs to facilitate mRNA localization to the outer mitochondrial membrane, potentially for site-specific or co-translational import. This role may link the presence of efficient mitochondrial protein import to mitochondrial quality control through the PINK1-Parkin pathway.