Mitochondrial genome-maintaining activity of mouse mitochondrial transcription factor A and its transcript isoform in Saccharomyces cerevisiae.
Mitochondrial genome-maintaining activity of mouse mitochondrial transcription factor A and its transcript isoform in Saccharomyces cerevisiae.
复制标题
酿酒酵母中小鼠线粒体转录因子 A 及其转录亚型的线粒体基因组维持活性。
DOI：
10.1016/j.gene.2011.05.032
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发表时间：
2011
期刊：
影响因子：
3.5
通讯作者：
Yoo,YoungHyun
中科院分区：
文献类型：
--
作者：
Yoon,YoungGeol;Koob,MichaelD;Yoo,YoungHyun
线粒体转录因子A（mitochondrialtranscription factor A，Tfam）是线粒体DNA（mitochondrialDNA，mtDNA）基因组中的一个重要转录因子，它与mtDNA结合形成线粒体类核（mitochondrialnucleoid，mt-nucleoid）结构，是mtDNA转录和维持所必需的。在这里，我们证明了小鼠Tfam和它的转录异构体（Tfamiso），它有一个较小的高迁移率族（HMG）-box 1域，使用酵母模型系统，其中包含一个删除的酵母同源物的小鼠Tfam蛋白，Abf 2 p的mtDNA组织活动。当小鼠Tfam基因被导入酵母基因组的ABF 2位点时，相应的小鼠蛋白Tfam和Tfamiso可以在功能上取代酵母Abf 2 p，并支持酵母中mtDNA的维持和线粒体生物合成。在表达小鼠蛋白的菌株和野生型酵母菌株中，mtDNA中编码的基因的生长特性、mtDNA含量和线粒体蛋白水平是相当的，这表明所述蛋白在酵母线粒体中具有稳健的mtDNA维持和表达功能。这些结果意味着小鼠线粒体类核蛋白的线粒体DNA组织活性在结构和进化上是保守的，因此它们可以维持远亲和截然不同物种（例如酵母）的线粒体DNA。
Mitochondrial transcription factor A (Tfam) binds to and organizes mitochondrial DNA (mtDNA) genome into a mitochondrial nucleoid (mt-nucleoid) structure, which is necessary for mtDNA transcription and maintenance. Here, we demonstrate the mtDNA-organizing activity of mouse Tfam and its transcript isoform (Tfamiso), which has a smaller high-mobility group (HMG)-box1 domain, using a yeast model system that contains a deletion of the yeast homolog of mouse Tfam protein, Abf2p. When the mouse Tfam genes were introduced into the ABF2 locus of yeast genome, the corresponding mouse proteins, Tfam and Tfamiso, can functionally replace the yeast Abf2p and support mtDNA maintenance and mitochondrial biogenesis in yeast. Growth properties, mtDNA content and mitochondrial protein levels of genes encoded in the mtDNA were comparable in the strains expressing mouse proteins and the wild-type yeast strain, indicating that the proteins have robust mtDNA-maintaining and -expressing function in yeast mitochondria. These results imply that the mtDNA-organizing activities of the mouse mt-nucleoid proteins are structurally and evolutionary conserved, thus they can maintain the mtDNA of distantly related and distinctively different species, such as yeast.