Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline
Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline
复制标题
DOI：
10.1074/jbc.m117.809970
复制
发表时间：
2017-11-10
影响因子：
4.8
通讯作者：
Henry, Susan A.
中科院分区：
文献类型：
--
作者：
Gaspar, Maria L.;Chang, Yu-Fang;Henry, Susan A.
在酿酒酵母中，Opi 1 p阻遏物通过Opi 1 p/Ino 2 p-Ino 4p调节回路控制INO 1的表达。肌醇耗竭有利于Opi 1 p与内质网（ER）膜上的Scs 2 p和磷脂酸相互作用。然而，肌醇补充有利于Opi 1 p从ER易位到细胞核中，在那里它与Ino 2 p-Ino 4p复合物相互作用，减弱INO 1的转录。利用缺乏Scs 2 p（scs 2）的菌株和缺乏与Scs 2 p相互作用的能力的突变体OPI 1FFAT来检查Opi 1 p-Scs 2 p相互作用在INO 1表达和总体脂质代谢的调节中的特定作用。Opi 1 p-Scs 2 p相互作用的丧失降低了INO 1的表达并赋予肌醇营养缺陷型。此外，缺乏这种相互作用的菌株中的肌醇耗竭导致Opi 1 p定位于脂滴形成的位点，与三酰甘油合成增加一致。补充胆碱肌醇耗尽的生长培养基导致TAG合成减少在所有三个菌株。然而，在缺乏Opi 1 p-Scs 2 p相互作用的菌株中，Opi 1 p保留在细胞核中，阻止INO 1的表达。这些数据支持的结论是，一个特定的池磷脂酸，与脂滴形成在核周的ER，是负责的Opi 1 p从细胞核到ER的初始快速退出，并需要在胆碱的存在下INO 1的表达。此外，在Opi 1 p-Scs 2 p相互作用受损的两种菌株中，ESTA特异性磷脂，心磷脂显着减少，表明这种相互作用是将磷脂酸从ER转移到线粒体进行心磷脂合成所必需的。
In the yeast Saccharomyces cerevisiae, the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1. A strain devoid of Scs2p (scs2) and a mutant, OPI1FFAT, lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1. These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis.