Department of Cell and Molecular Biology, University of Gothenburg, S-405 30 Gothenburg, Sweden.
Lipids Health Dis. 2011 Dec 28;10:243. doi: 10.1186/1476-511X-10-243.
The mevalonate pathway in human is responsible for the synthesis of cholesterol and other important biomolecules such as coenzyme Q, dolichols and isoprenoids. These molecules are required in the cell for functions ranging from signaling to membrane integrity, protein prenylation and glycosylation, and energy homeostasis. The pathway consists of a main trunk followed by sub-branches that synthesize the different biomolecules. The majority of our knowledge about the mevalonate pathway is currently focused on the cholesterol synthesis branch, which is the target of the cholesterol-lowering statins; less is known about the function and regulation of the non-cholesterol-related branches. To study them, we need a biological system where it is possible to specifically modulate these metabolic branches individually or in groups. The nematode Caenorhabditis elegans (C. elegans) is a promising model to study these non-cholesterol branches since its mevalonate pathway seems very well conserved with that in human except that it has no cholesterol synthesis branch. The simple genetic makeup and tractability of C. elegans makes it relatively easy to identify and manipulate key genetic components of the mevalonate pathway, and to evaluate the consequences of tampering with their activity. This general experimental approach should lead to new insights into the physiological roles of the non-cholesterol part of the mevalonate pathway. This review will focus on the current knowledge related to the mevalonate pathway in C. elegans and its possible applications as a model organism to study the non-cholesterol functions of this pathway.
人体内的甲羟戊酸途径负责合成胆固醇和其他重要生物分子,如辅酶 Q、多萜醇和异戊二烯。这些分子在细胞中参与从信号转导到膜完整性、蛋白质 prenylation 和糖基化以及能量稳态等各种功能。该途径由一个主干和几个分支组成,这些分支合成不同的生物分子。目前,我们对甲羟戊酸途径的了解主要集中在胆固醇合成分支上,该分支是降胆固醇他汀类药物的作用靶点;而对非胆固醇相关分支的功能和调节了解较少。为了研究它们,我们需要一个能够单独或分组调节这些代谢分支的生物系统。秀丽隐杆线虫(C. elegans)是研究这些非胆固醇分支的一种很有前途的模型,因为它的甲羟戊酸途径与人类非常相似,除了没有胆固醇合成分支。秀丽隐杆线虫的简单遗传组成和易于处理性使得识别和操纵甲羟戊酸途径的关键遗传成分相对容易,并评估干扰其活性的后果。这种通用的实验方法应该会为甲羟戊酸途径中非胆固醇部分的生理作用提供新的见解。本文综述了与 C. elegans 中甲羟戊酸途径相关的最新知识,以及它作为研究该途径中非胆固醇功能的模型生物的可能应用。
Lipids Health Dis. 2011-12-28
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