Department of Chemistry, Faculty of Sciences, Kyushu University, 744, Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Sci Rep. 2020 Jul 1;10(1):10792. doi: 10.1038/s41598-020-67734-8.
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 yeast Saccharomyces cerevisiae are 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 to sur1∆ 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.
所有生物体都有应激反应系统来保护自己免受各种环境压力的影响，并且膜脂的调节被认为在获得应激耐受性方面起着重要作用。酵母酿酒酵母中的复杂鞘脂根据极性头部基团结构的差异分为三种类型，生物膜中复杂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（sur1∆ csh1∆）导致的肌醇磷酸神经酰胺（IPCs）积累，即复杂鞘脂组成的平衡被打破，导致对低 pH 条件（pH 4.0-2.5）的敏感性增加。此外，对 sur1∆ csh1∆细胞进行低 pH 抗性的抑制突变筛选显示，质膜中麦角固醇稳态的变化可以挽救这种敏感性，表明在低 pH 条件下复杂鞘脂和麦角固醇之间存在功能关系。在低 pH 条件下，野生型酵母细胞中 IPC 水平降低，并且强制增强 IPC 的生物合成会导致低 pH 敏感性增加。因此，推测在低 pH 条件下 IPC 的积累对酵母有害，IPC 水平的下调是适应低 pH 条件的机制之一。
