Regulation by thyroid hormone of nuclear and mitochondrial genes encoding subunits of cytochrome-c oxidase in rat liver and skeletal muscle.
Regulation by thyroid hormone of nuclear and mitochondrial genes encoding subunits of cytochrome-c oxidase in rat liver and skeletal muscle.
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DOI：
10.1210/mend.6.9.1331777
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发表时间：
1992-09
影响因子：
--
通讯作者：
R. J. Wiesner;T T Kurowski-T;R. Zak
中科院分区：
文献类型：
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作者：
R. J. Wiesner;T T Kurowski-T;R. Zak
线粒体的生物发生涉及位于核染色体和线粒体DNA上的基因的表达。我们通过改变动物的甲状腺状态来改变大鼠肌肉和肝脏的线粒体含量，通过检测细胞核(IV、Va和Vic)和线粒体(II和III)亚单位的细胞色素-c氧化酶的转录水平来研究这两个基因组的协调。在甲状腺功能低下的动物中，这些mRNAs的组织水平普遍下降，在甲状腺激素(T3)治疗后再次上调。然而，在T3处理后24小时，肝脏中所有核转录本的水平显著增加，但肌肉中的转录本水平延迟或保持不变(Vic)。相比之下，线粒体转录本的水平在肌肉中较早升高，在肝脏中较晚。通过免疫印迹分析，相应多肽的丰度随着其mRNAs的变化而在方向和幅度上发生变化，表明翻译前控制。我们得出的结论是，这两个基因组不是通过共同的协调机制，而是通过两条不同的途径，以组织特异性的动力学方式对T3进行调节。S1-核酸酶保护分析表明，在两个组织中可能只有一个Vic亚单位的转录本，从而排除了组织特异性反应是由于两个同源基因表达的可能性。尽管观察到线粒体转录本的变化，但线粒体DNA的丰度没有改变，这表明线粒体基因的表达是由转录机制调节的，而不是像其他人假设的那样受基因剂量的影响。
Biogenesis of mitochondria involves the expression of genes located on nuclear chromosomes as well as on mitochondrial DNA. We studied the coordination of the two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the mitochondrial content of rat muscle and liver by altering the thyroid state of the animals. Tissue levels of these mRNAs were generally decreased in hypothyroid animals and were up-regulated again after thyroid hormone (T3) treatment. However, significant increases in the levels of all nuclear transcripts were observed in the liver 24 h after T3 treatment, but were delayed or remained unaltered (VIc) in muscle. In contrast, levels of mitochondrial transcripts were elevated early in muscle and late in liver. The abundance of the corresponding polypeptides, which were analyzed by immunoblotting, changed in direction and magnitude according to the changes in their mRNAs, indicating pretranslational control. We conclude that the two genomes are regulated by T3 not through a common coordinating mechanism, but via two separate pathways, which respond to T3 with tissue-specific kinetics. S1-nuclease protection analysis showed that probably only one transcript for subunit VIc is present in both tissues, thus excluding the possibility that the tissue-specific response is due to the expression of two isogenes. The abundance of mitochondrial DNA was unaltered despite the observed changes in mitochondrial transcripts, indicating that mitochondrial gene expression is regulated by transcriptional mechanisms and not by gene dosage as has been postulated by others.