The S-cerevisiae HAP complex, a key regulator of mitochondrial function, coordinates nuclear and mitochondrial gene expression

The S-cerevisiae HAP complex, a key regulator of mitochondrial function, coordinates nuclear and mitochondrial gene expression
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DOI:
10.1002/cfg.254
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发表时间:
2003-02-01
影响因子:
--
通讯作者:
Bolotin-Fukuhara, M
Bolotin-Fukuhara, M
中科院分区:
其他
文献类型:
--
作者:
Buschlen, S;Amillet, JM;Bolotin-Fukuhara, M

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我们已经比较了酿酒酵母全局基因表达的野生型和突变体(Ahap2和Ahap4)的HAP转录复合物,这已被证明是必要的呼吸基质上的生长。几百个ORF正或负控制的这个复杂的,我们在这里详细分析的影响HAP对线粒体。我们发现野生型菌株中大多数上调的基因参与细胞器功能,但几乎没有下调的基因。正如预期的那样,编码呼吸链复合物不同亚基的核基因在野生型中的表达比突变体中的表达更多,但在这组中,我们还发现了线粒体翻译装置的关键组成部分。线粒体翻译的这种控制可能是在阐述呼吸链中协调线粒体和核基因表达的手段之一。此外,HAP控制参与其他几个线粒体过程(输入,线粒体分裂)的核基因,这些过程定义了细胞的代谢状态,但不控制线粒体DNA的复制和转录。在大多数情况下,一个假定的CCAAT结合位点存在于ORF的上游,而在其他情况下没有这样的位点存在,这表明控制是间接的。HAP复合物调节的大量基因,以及HAP还调节一些功能未知的假定转录激活因子的事实,将该复合物置于细胞的全局转录调节中的高层次位置。版权所有(C)2003约翰威利父子有限公司。
We have compared Saccharomyces cerevisiae global gene expression in wild-type and mutants (Ahap2 and Ahap4) of the HAP transcriptional complex, which has been shown to be necessary for growth on respiratory substrates. Several hundred ORFs are under positive or negative control of this complex and we analyse here in detail the effect of HAP on mitochondria. We found that most of the genes upregulated in the wild-type strain were involved in organelle functions, but practically none of the downregulated ones. Nuclear genes encoding the different subunits of the respiratory chain complexes figure in the genes more expressed in the wild-type than in the mutants, as expected, but in this group we also found key components of the mitochondrial translation apparatus. This control of mitochondrial translation may be one of the means of coordinating mitochondrial and nuclear gene expression in elaborating the respiratory chain. In addition, HAP controls the nuclear genes involved in several other mitochondrial processes (import, mitochondrial division) that define the metabolic state of the cell, but not mitochondrial DNA replication and transcription. In most cases, a putative CCAAT-binding site is present upstream of the ORF, while in others no such sites are present, suggesting the control to be indirect. The large number of genes regulated by the HAP complex, as well as the fact that HAP also regulates some putative transcriptional activators of unknown function, place this complex at a hierarchically high position in the global transcriptional regulation of the cell. Copyright (C) 2003 John Wiley Sons, Ltd.