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协调储存脂质合成和膜生物发生:三酰基甘油代谢与磷脂酰肌醇合成之间相互交流的证据。

Coordination of storage lipid synthesis and membrane biogenesis: evidence for cross-talk between triacylglycerol metabolism and phosphatidylinositol synthesis.

机构信息

Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.

出版信息

J Biol Chem. 2011 Jan 21;286(3):1696-708. doi: 10.1074/jbc.M110.172296. Epub 2010 Oct 23.

Abstract

Despite the importance of triacylglycerols (TAG) and steryl esters (SE) in phospholipid synthesis in cells transitioning from stationary-phase into active growth, there is no direct evidence for their requirement in synthesis of phosphatidylinositol (PI) or other membrane phospholipids in logarithmically growing yeast cells. We report that the dga1Δlro1Δare1Δare2Δ strain, which lacks the ability to synthesize both TAG and SE, is not able to sustain normal growth in the absence of inositol (Ino(-) phenotype) at 37 °C especially when choline is present. Unlike many other strains exhibiting an Ino(-) phenotype, the dga1Δlro1Δare1Δare2Δ strain does not display a defect in INO1 expression. However, the mutant exhibits slow recovery of PI content compared with wild type cells upon reintroduction of inositol into logarithmically growing cultures. The tgl3Δtgl4Δtgl5Δ strain, which is able to synthesize TAG but unable to mobilize it, also exhibits attenuated PI formation under these conditions. However, unlike dga1Δlro1Δare1Δare2Δ, the tgl3Δtgl4Δtgl5Δ strain does not display an Ino(-) phenotype, indicating that failure to mobilize TAG is not fully responsible for the growth defect of the dga1Δlro1Δare1Δare2Δ strain in the absence of inositol. Moreover, synthesis of phospholipids, especially PI, is dramatically reduced in the dga1Δlro1Δare1Δare2Δ strain even when it is grown continuously in the presence of inositol. The mutant also utilizes a greater proportion of newly synthesized PI than wild type for the synthesis of inositol-containing sphingolipids, especially in the absence of inositol. Thus, we conclude that storage lipid synthesis actively influences membrane phospholipid metabolism in logarithmically growing cells.

摘要

尽管三酰基甘油(TAG)和甾醇酯(SE)在细胞从静止期进入活跃生长时合成磷脂具有重要意义,但没有直接证据表明它们在对数生长期酵母细胞中合成磷脂酰肌醇(PI)或其他膜磷脂是必需的。我们报告说,缺乏合成 TAG 和 SE 能力的 dga1Δlro1Δare1Δare2Δ 菌株在 37°C 时不能在没有肌醇(Ino(-)表型)的情况下维持正常生长,尤其是当存在胆碱时。与许多表现出 Ino(-)表型的其他菌株不同,dga1Δlro1Δare1Δare2Δ 菌株在 INO1 表达方面没有缺陷。然而,与野生型细胞相比,突变体在向对数生长期培养物中重新引入肌醇时,PI 含量的恢复较慢。能够合成 TAG 但不能动员它的 tgl3Δtgl4Δtgl5Δ 菌株在这些条件下也表现出 PI 形成减弱。然而,与 dga1Δlro1Δare1Δare2Δ 菌株不同,tgl3Δtgl4Δtgl5Δ 菌株不表现出 Ino(-)表型,这表明无法动员 TAG 不能完全解释 dga1Δlro1Δare1Δare2Δ 菌株在没有肌醇的情况下的生长缺陷。此外,即使在持续存在肌醇的情况下生长,dga1Δlro1Δare1Δare2Δ 菌株的磷脂,特别是 PI 的合成也显著减少。该突变体还比野生型细胞更多地利用新合成的 PI 来合成含肌醇的鞘脂,尤其是在没有肌醇的情况下。因此,我们得出结论,储存脂质的合成积极影响对数生长期细胞的膜磷脂代谢。

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