Mitochondrial genomes are retained by selective constraints on protein targeting
Mitochondrial genomes are retained by selective constraints on protein targeting
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DOI：
10.1073/pnas.1421372112
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发表时间：
2015-08-18
影响因子：
11.1
通讯作者：
Andersson, Siv G. E.
中科院分区：
文献类型：
--
作者：
Bjorkholm, Patrik;Harish, Ajith;Andersson, Siv G. E.
线粒体是细菌来源的真核细胞中产生能量的细胞器。线粒体基因组在基因含量最小化的选择下进化，但不知道为什么不是所有的线粒体基因都转移到核基因组中。在这里，我们预测，由线粒体基因组编码的疏水膜蛋白将被识别的信号识别颗粒，并针对内质网，如果它们是核编码和在细胞质中翻译。HeLa细胞的细胞质中的细胞色素氧化酶亚基1、脱辅基细胞色素B和ATP合酶亚基6的细胞编码蛋白质的表达证实了输出到内质网。为了研究线粒体蛋白质组在真核细胞内受到选择性限制的程度，我们研究了细菌和真核生物中线粒体蛋白质结构域的发生。氧化磷酸化系统的辅助蛋白质结构域是线粒体所特有的，表明新蛋白质折叠的进化。大多数在核糖体辅助蛋白中鉴定的结构域也在其他功能和位置的真核蛋白中发现。总的来说，在线粒体蛋白中鉴定的蛋白质结构域中有三分之一在细菌中很少发现。我们的结论是，线粒体基因组一直保持，以确保正确定位的高度疏水性膜蛋白。两者合计，结果表明，对真核细胞的选择性限制在调节线粒体基因组和蛋白质组的进化中发挥了重要作用。
Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome.