Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine and cardiolipin biosynthetic pathways in Saccharomyces cerevisiae
Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine and cardiolipin biosynthetic pathways in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m505478200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Greenberg, ML
中科院分区：
文献类型：
--
作者：
Gohil, VM;Thompson, MN;Greenberg, ML
酿酒酵母线粒体含有合成磷脂心磷脂（CL）和磷脂酰乙醇胺（PE）所需的酶，这些酶在线粒体膜中富集。以往的研究表明，PE可以弥补CL的缺乏，反之亦然。这些数据表明，PE和CL有重叠的功能，这两种脂质的情况下可能是致命的。为了解决这一假设，我们确定是否crd1德尔塔突变体，缺乏CL，是可行的，在遗传背景中，PE合成被遗传阻断。线粒体PE途径基因PSD1的缺失与crd1 Delta突变体是合成致死性的，而高尔基体和内质网途径基因PSD2和DPL1的缺失没有导致合成致死性。磷脂酰胆碱减少20倍并不影响crd1 δ细胞的生长。补充乙醇胺，这导致增加的PE合成，或补充丙醇胺，这导致新的磷脂磷脂酰丙醇胺的合成，未能挽救crd 1 Delta psd 1 Delta细胞的合成致死性。这些结果表明，线粒体生物合成的PE是必不可少的酵母突变体缺乏CL的生存能力。
Saccharomyces cerevisiae mitochondria contain enzymes required for synthesis of the phospholipids cardiolipin ( CL) and phosphatidylethanolamine ( PE), which are enriched in mitochondrial membranes. Previous studies indicated that PE may compensate for the lack of CL, and vice versa. These data suggest that PE and CL have overlapping functions and that the absence of both lipids may be lethal. To address this hypothesis, we determined whether the crd1 Delta mutant, which lacks CL, was viable in genetic backgrounds in which PE synthesis was genetically blocked. Deletion of the mitochondrial PE pathway gene PSD1 was synthetically lethal with the crd1 Delta mutant, whereas deletion of the Golgi and endoplasmic reticulum pathway genes PSD2 and DPL1 did not result in synthetic lethality. A 20- fold reduction in phosphatidylcholine did not affect the growth of crd1 Delta cells. Supplementation with ethanolamine, which led to increased PE synthesis, or with propanolamine, which led to synthesis of the novel phospholipid phosphatidylpropanolamine, failed to rescue the synthetic lethality of the crd1 Delta psd1 Delta cells. These results suggest that mitochondrial biosynthesis of PE is essential for the viability of yeast mutants lacking CL.