DGK1-encoded Diacylglycerol Kinase Activity Is Required for Phospholipid Synthesis during Growth Resumption from Stationary Phase in Saccharomyces cerevisiae
DGK1-encoded Diacylglycerol Kinase Activity Is Required for Phospholipid Synthesis during Growth Resumption from Stationary Phase in Saccharomyces cerevisiae
复制标题
DOI：
10.1074/jbc.m110.194308
复制
发表时间：
2011-01-14
影响因子：
4.8
通讯作者：
Carman, George M.
中科院分区：
文献类型：
--
作者：
Fakas, Stylianos;Konstantinou, Chrysanthos;Carman, George M.
在酿酒酵母中，磷脂合成的三酰甘油动员发生在从稳定期恢复生长期间，并且这种代谢在缺乏脂肪酸从头合成的情况下是必需的。在这项工作中，我们提供的证据表明，DGK1 编码的二酰甘油激酶活性是将三酰甘油衍生的二酰甘油转化为磷脂酸以进行磷脂合成所必需的。缺乏二酰基甘油激酶活性（例如 dgk1 Delta 突变）的细胞在脂肪酸合成抑制剂浅蓝素存在下无法恢复生长。脂质分析数据显示，dgk1 Delta 突变细胞不动员三酰甘油进行膜磷脂合成，而是积累了二酰甘油。通过阻止 PAH1 编码的磷脂酸磷酸酶形成二酰甘油以及通过肯尼迪途径将二酰甘油引导至磷脂酰胆碱，对 dgk1 Delta 表型进行了部分补充。这些观察结果与二辛酰基-二酰基甘油对野生型细胞生长的抑制作用相结合，表明二酰基甘油激酶还具有减轻二酰基甘油毒性的功能。
In the yeast Saccharomyces cerevisiae, triacylglycerol mobilization for phospholipid synthesis occurs during growth resumption from stationary phase, and this metabolism is essential in the absence of de novo fatty acid synthesis. In this work, we provide evidence that DGK1-encoded diacylglycerol kinase activity is required to convert triacylglycerol-derived diacylglycerol to phosphatidate for phospholipid synthesis. Cells lacking diacylglycerol kinase activity (e.g. dgk1 Delta mutation) failed to resume growth in the presence of the fatty acid synthesis inhibitor cerulenin. Lipid analysis data showed that dgk1 Delta mutant cells did not mobilize triacylglycerol for membrane phospholipid synthesis and accumulated diacylglycerol. The dgk1 Delta phenotypes were partially complemented by preventing the formation of diacylglycerol by the PAH1-encoded phosphatidate phosphatase and by channeling diacylglycerol to phosphatidylcholine via the Kennedy pathway. These observations, coupled to an inhibitory effect of dioctanoyl-diacylglycerol on the growth of wild type cells, indicated that diacylglycerol kinase also functions to alleviate diacylglycerol toxicity.