Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid
Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid
复制标题
DOI：
10.1126/science.1096083
复制
发表时间：
2004-06-11
期刊：
影响因子：
56.9
通讯作者：
Levine, TP
中科院分区：
文献类型：
--
作者：
Loewen, CJR;Gaspar, ML;Levine, TP
细胞通过协调合成不同种类的脂质来调节其膜的生物物理性质。在这里，我们确定了一个高度动态的反馈机制，芽殖酵母酿酒酵母可以调节磷脂的生物合成。内质网上的磷脂酸直接与可溶性转录抑制因子Opi1p结合，使其在核外保持无活性。在加入脂质前体肌醇后，这种磷脂酸被迅速消耗，从内质网释放Opi1p，并允许其核转位和靶基因的抑制。因此，磷脂酸似乎是一种必需的普遍存在的代谢中间体和信号脂质。
Cells regulate the biophysical properties of their membranes by coordinated synthesis of different classes of lipids. Here, we identified a highly dynamic feedback mechanism by which the budding yeast Saccharomyces cerevisiae can regulate phospholipid biosynthesis. Phosphatidic acid on the endoplasmic reticulum directly bound to the soluble transcriptional repressor Opi1p to maintain it as inactive outside the nucleus. After the addition of the lipid precursor inositol, this phosphatidic acid was rapidly consumed, releasing Opi1p from the endoplasmic reticulum and allowing its nuclear translocation and repression of target genes. Thus, phosphatidic acid appears to be both an essential ubiquitous metabolic intermediate and a signaling lipid.