Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast
Oleate Inhibits Steryl Ester Synthesis and Causes Liposensitivity in Yeast
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DOI：
10.1074/jbc.m110.122085
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发表时间：
2010-08-27
影响因子：
4.8
通讯作者：
Daum, Guenther
中科院分区：
文献类型：
--
作者：
Connerth, Melanie;Czabany, Tibor;Daum, Guenther
在酿酒酵母中，中性脂质可以通过四种酰基转移酶合成，即Dga1p和Lro1p产生三酰基甘油(TAG)以及Are1p和Are2p形成甾醇酯(SE)。 TAG 和 SE 储存在称为脂质颗粒/液滴的细胞器中。酵母细胞在补充油酸的培养基上生长强烈诱导脂质颗粒的增殖，特别是 TAG 的合成，TAG 是过量脂肪酸的主要库。令人惊讶的是，SE 合成在这些条件下受到强烈抑制。在这里，我们表明这种效应并不是由于转录水平上编码主要酵母 SE 合酶的 ARE2 表达减少所致，而是由于游离油酸对 Are2p 的竞争性酶促抑制所致。因此，在油酸盐上生长的三重突变体 dga1 Delta lro1 Delta are1 Delta ARE2(+) 没有形成大量的 SE，并表现出与 dga1 Delta lro1 Delta are1 Delta are2(+) 四重突变体相似的生长表型，包括缺乏脂质颗粒。这些突变体在油酸上的生长被严重延迟，细胞活力降低，但通过适应得以恢复。在这些菌株中，油酸应激引起细胞内膜的形态变化、磷脂组成的改变以及额外的脂质类别——脂肪酸乙酯的形成。总之，我们的数据表明，接触油酸会导致脂质和膜稳态紊乱以及酵母的脂敏感性。
In the yeast Saccharomyces cerevisiae, neutral lipids can be synthesized by four acyltransferases, namely Dga1p and Lro1p producing triacylglycerols (TAG) and Are1p and Are2p forming steryl esters (SE). TAG and SE are stored in an organelle called lipid particles/droplet. Growth of yeast cells on oleate-supplemented media strongly induced proliferation of lipid particles and specifically the synthesis of TAG, which serve as the major pool for the excess of fatty acids. Surprisingly, SE synthesis was strongly inhibited under these conditions. Here, we show that this effect was not due to decreased expression of ARE2 encoding the major yeast SE synthase at the transcriptional level but to competitive enzymatic inhibition of Are2p by free oleate. Consequently, a triple mutant dga1 Delta lro1 Delta are1 Delta ARE2(+) grown on oleate did not form substantial amounts of SE and exhibited a growth phenotype similar to the dga1 Delta lro1 Delta are1 Delta are2(+) quadruple mutant, including lack of lipid particles. Growth of these mutants on oleate was strongly delayed, and cell viability was decreased but rescued by adaptation. In these strains, oleate stress caused morphological changes of intracellular membranes, altered phospholipid composition and formation of an additional lipid class, ethyl esters of fatty acids. In summary, our data showed that exposure to oleate led to disturbed lipid and membrane homeostasis along with liposensitivity of the yeast.