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首页> 外文期刊>Molecular and Cellular Biology >A Variant Form of the Nuclear Triiodothyronine Receptor c-ErbAα1 Plays a Direct Role in Regulation of Mitochondrial RNA Synthesis
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A Variant Form of the Nuclear Triiodothyronine Receptor c-ErbAα1 Plays a Direct Role in Regulation of Mitochondrial RNA Synthesis

机译：核三碘甲状腺氨酸受体c-ErbAα1的变体形式在线粒体RNA合成调控中发挥直接作用。

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In earlier research, we identified a 43-kDa c-ErbAα1 protein (p43) in the mitochondrial matrix of rat liver. In the present work, binding experiments indicate that p43 displays an affinity for triiodothyronine (T3) similar to that of the T3 nuclear receptor. Using in organello import experiments, we found that p43 is targeted to the organelle by an unusual process similar to that previously reported for MTF1, a yeast mitochondrial transcription factor. DNA-binding experiments demonstrated that p43 specifically binds to four mitochondrial DNA sequences with a high similarity to nuclear T3 response elements (mt-T3REs). Using in organello transcription experiments, we observed that p43 increases the levels of both precursor and mature mitochondrial transcripts and the ratio of mRNA to rRNA in a T3-dependent manner. These events lead to stimulation of mitochondrial protein synthesis. In transient-transfection assays with reporter genes driven by the mitochondrial D loop or two mt-T3REs located in the D loop, p43 stimulated reporter gene activity only in the presence of T3. All these effects were abolished by deletion of the DNA-binding domain of p43. Finally, p43 overexpression in QM7 cells increased the levels of mitochondrial mRNAs, thus indicating that the in organello influence of p43 was physiologically relevant. These data reveal a novel hormonal pathway functioning within the mitochondrion, involving a truncated form of a nuclear receptor acting as a potent mitochondrial T3-dependent transcription factor.
机译：在较早的研究中，我们在大鼠肝脏的线粒体基质中鉴定出一种43 kDac-ErbAα1蛋白（p43）。在目前的工作中，结合实验表明，p43对三碘甲状腺素（T3）的亲和力与T3核受体的亲和力相似。在器官移植的导入实验中，我们发现p43通过与之前报道的酵母线粒体转录因子MTF1类似的异常过程靶向细胞器。 DNA结合实验表明，p43与四个线粒体DNA序列特异性结合，与核T3反应元件（mt-T3REs）具有高度相似性。通过在Organello转录实验中使用，我们观察到p43以T3依赖性方式增加了前体和成熟线粒体转录本的水平以及mRNA与rRNA的比率。这些事件导致线粒体蛋白质合成的刺激。在利用由线粒体D环或位于D环中的两个mt-T3RE驱动的报告基因进行的瞬时转染测定中，p43仅在存在T3的情况下刺激报告基因的活性。通过删除p43的DNA结合结构域消除了所有这些作用。最后，p43在QM7细胞中的过表达增加了线粒体mRNA的水平，因此表明p43在细胞内的影响与生理相关。这些数据揭示了在线粒体内起作用的新型激素途径，涉及截短形式的核受体，其充当有效的线粒体T3依赖性转录因子。

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