The mitochondrial pool of free amino acids reflects the composition of mitochondrial DNA-encoded proteins: indication of a post- translational quality control for protein synthesis.

The mitochondrial pool of free amino acids reflects the composition of mitochondrial DNA-encoded proteins: indication of a post- translational quality control for protein synthesis.
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游离氨基酸的线粒体池反映线粒体DNA编码蛋白的组成:指示蛋白质合成后翻译后质量控制。

DOI:
10.1042/bsr20080090
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发表时间:
2008-10
期刊:
影响因子:
4
通讯作者:
Giulivi C
Giulivi C
中科院分区:
生物学3区
文献类型:
--
作者:
Ross-Inta C;Tsai CY;Giulivi C

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线粒体可以利用自身的生物合成机制合成mtDNA编码的有限数量的蛋白质,而大多数蛋白质是从细胞质中输入的。可以假设线粒体氨基酸库遵循mtdna编码蛋白质中氨基酸的频率,或者,该谱是氨基酸参与蛋白质合成以外的途径(例如血红素生物合成,转氨酶反应)的结果。这些假设是通过评估高偶联纯化肝线粒体中的游离氨基酸和衍生物库来验证的,这些线粒体来自营养充足的生长饲料喂养的大鼠。我们的研究结果表明,该池主要反映了mtdna编码蛋白的氨基酸组成,这表明蛋白质合成存在翻译后控制。这一结论得到了以下结果的支持:1 .基质中游离氨基酸的浓度与mtdna编码蛋白中氨基酸丰度的频率之间存在相关性;二是mtdna编码的蛋白质和线粒体氨基酸库中必需与非必需氨基酸的比例相似;第三,密码子使用或tRNA水平与氨基酸浓度之间缺乏相关性。关于哺乳动物线粒体氨基酸含量的定量信息,如本报告中提出的,以及功能研究将帮助我们更好地了解线粒体疾病的发病机制或线粒体代谢的生化意义。
Mitochondria can synthesize a limited number of proteins encoded by mtDNA by using its own biosynthetic machinery, whereas most of the proteins are imported from the cytosol. It could be hypothesized that the mitochondrial pool of amino acids follows the frequency of amino acids in mtDNA-encoded proteins or alternatively, the profile is the result of the participation of amino acids in pathways other than protein synthesis (e.g. heme biosynthesis, aminotransferase reactions). These hypotheses were tested by evaluating the pool of free amino acids and derivatives in highly-coupled, purified liver mitochondria obtained from rats fed a nutritionally adequate diet for growth. Our results indicated that the pool mainly reflects the amino acid composition of mtDNA-encoded proteins suggesting that there is a posttranslational control of protein synthesis. This conclusion was supported by the following findings: one, correlation between the concentration of free amino acids in the matrix and the frequency of abundance of amino acids in mtDNA-encoded proteins; two, the similar ratios of essential-to-nonessential amino acids in mtDNA-encoded proteins and mitochondrial pool of amino acids; three, lack of a correlation between codon usage or tRNA levels and amino acid concentrations. Quantitative information on the mammalian mitochondrial content of amino acids, such as that presented in this report, along with functional studies will help us better understand the pathogenesis of mitochondrial diseases or the biochemical implications in mitochondrial metabolism.