The regulation of COQ5 gene expression by energy source
The regulation of COQ5 gene expression by energy source
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DOI：
10.1080/10715760290021360
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发表时间：
2002-04-01
影响因子：
3.3
通讯作者：
Willis, RA
中科院分区：
文献类型：
--
作者：
Hagerman, RA;Trotter, PJ;Willis, RA
心肌病的严重程度与辅酶Q（Q）的组织水平呈负相关，表明Q合成可能影响疾病的进展。有人认为，Q作为一种内源性合成的抗氧化剂，除了再生有效的抗氧化剂，维生素E和C。然而，很少有人知道的机制，调节Q合成。以简单的真核生物酿酒酵母（Saccharomycescerevisiae）为模型，设计实验从基因水平研究Q合成的调控。为了研究能量来源对COQ 5基因表达的调节，在用葡萄糖、甘油或油酸处理的酵母细胞中评估mRNA含量。1.5小时后，油酸处理的细胞产生的COQ 5 mRNA比甘油处理的细胞产生的更多。使用COQ 5启动子缺失/报告基因构建体进行的实验证明了对油酸的特异性应答。额外的启动子缺失分析表明，nonfermentable碳源元素也存在，响应甘油和油酸。特定的油酸反应似乎受到转录因子Rtg家族的调节。该蛋白质家族是油酸诱导的β-氧化和过氧化物酶体增殖基因表达所必需的，并且在协调响应油酸的线粒体/过氧化物酶体/核通讯以及细胞呼吸缺陷中起重要作用。
The degree of severity of cardiomyopathy is inversely correlated with tissue levels of coenzyme Q (Q), suggesting that Q synthesis may impact the progression of the disease. It has been suggested that Q functions as an endogenously synthesized anti-oxidant, in addition to regenerating the potent anti-oxidants, vitamins E and C. However, very little is known about the mechanisms that regulate Q synthesis. Using the simple eukaryote Saccharomyces cerevisiae as a model, experiments have been designed to investigate the regulation of Q synthesis at the genetic level. To investigate the regulation of COQ5 gene expression by energy source, mRNA content was evaluated in yeast cells treated with dextrose, glycerol or oleic acid. After 1.5 h, more COQ5 mRNA is produced by oleic acid treated cells than by glycerol treated. Experiments performed using COQ5 promoter deletion/reporter constructs demonstrate a specific response to oleic acid. Additional promoter deletion analysis demonstrates that a nonfermentable carbon source element is also present, responding to both glycerol and oleic acid. The specific oleic acid response appears to be regulated by the Rtg family of transcription factors. This family of proteins is required for oleic acid-induced expression of genes of beta-oxidation and peroxisomal proliferation, and plays an important role in co-ordinating mitochondrial/peroxisomal/nuclear communication in response to oleic acid, as well as defects in cellular respiration.