Proper regulation of inositolphosphorylceramide levels is required for acquirement of low pH resistance in budding yeast
Proper regulation of inositolphosphorylceramide levels is required for acquirement of low pH resistance in budding yeast
复制标题
芽殖酵母获得低 pH 抗性需要适当调节肌醇磷酸神经酰胺水平
DOI：
10.1038/s41598-020-67734-8
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
and Tani M.
中科院分区：
文献类型：
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作者：
Otsu M;Toume M;Yamaguchi Y;and Tani M.
所有生物都有应激反应系统来保护自己免受各种环境胁迫，膜脂的调节被认为在获得胁迫耐受性中起重要作用。酵母菌中的复合鞘脂根据极性头基结构的差异分为三种类型，生物膜中复合鞘脂的组成和数量受到严格调节。在这项研究中，我们发现由于甘露糖肌醇磷酸神经酰胺生物合成缺陷（sur 1 β csh 1 β），即，复合鞘脂组成平衡的破坏导致对低pH条件（pH 4.0-2.5）的超敏反应。此外，筛选的抑制突变，赋予低pH值的抗性tosur 1csh 1csh细胞显示，麦角固醇在质膜稳态的变化可以挽救超敏反应，表明复杂的鞘脂和麦角固醇在低pH值条件下的功能关系。在低pH条件下，野生型酵母细胞表现出IPC水平的降低，并且IPC的生物合成的强制增强导致低pH超敏性。因此，这表明IPC的积累在低pH条件下对酵母是有害的，IPC水平的下调是低pH条件的适应机制之一。
All organisms have stress response systems to protect themselves from various environmental stresses, and regulation of membrane lipids is thought to play an important role in acquirement of stress tolerance. Complex sphingolipids in the yeastSaccharomyces cerevisiaeare classified into three types based on differences in the structure of the polar head group, and the compositions and quantities of complex sphingolipids in biomembranes are tightly regulated. In this study, we found that the accumulation of inositol phosphorylceramides (IPCs) due to a defect of mannosylinositol phosphorylceramide biosynthesis (sur1∆ csh1∆), i.e., disruption of the balance of the composition of complex sphingolipids, causes hypersensitivity to low pH conditions (pH 4.0–2.5). Furthermore, screening of suppressor mutations that confer low pH resistance tosur1∆ csh1∆cells revealed that a change in ergosterol homeostasis at plasma membranes can rescue the hypersensitivity, suggesting the functional relationship between complex sphingolipids and ergosterol under low pH conditions. Under low pH conditions, wild-type yeast cells exhibited decreases in IPC levels, and forced enhancement of the biosynthesis of IPCs causes low pH hypersensitivity. Thus, it was suggested that the accumulation of IPCs is detrimental to yeast under low pH conditions, and downregulation of IPC levels is one of the adaptation mechanisms for low pH conditions.