Lipid homeostasis allows cells to adjust membrane biophysical properties in response to changes in environmental conditions. In the yeast Saccharomyces cerevisiae, a downward shift in temperature from an optimal reduces membrane fluidity, which triggers a lipid remodeling of the plasma membrane. How changes in membrane fluidity are perceived, and how the abundance and composition of different lipid classes is properly balanced, remain largely unknown. Here, we show that the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], the most abundant plasma membrane phosphoinositide, drop rapidly in response to a downward shift in temperature. This change triggers a signaling cascade transmitted to cytosolic diphosphoinositol phosphate derivatives, among them 5-PP-IP4 and 1-IP7, that exert regulatory functions on genes involved in the inositol and phospholipids (PLs) metabolism, and inhibit the activity of the protein kinase Pho85. Consistent with this, cold exposure triggers a specific program of neutral lipids and PLs changes. Furthermore, we identified Pho85 as playing a key role in controlling the synthesis of long-chain bases (LCBs) via the Ypk1-Orm2 regulatory circuit. We conclude that Pho85 orchestrates a coordinated response of lipid metabolic pathways that ensure yeast thermal adaptation.

中文翻译：

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Pho85 和 PI(4,5)P2 调节不同的脂质代谢途径以应对寒冷。

脂质稳态允许细胞调整膜生物物理特性以响应环境条件的变化。在酿酒酵母中，温度从最佳温度向下转变会降低膜的流动性，从而引发质膜的脂质重塑。如何感知膜流动性的变化，以及如何适当平衡不同脂质类别的丰度和组成，仍然很大程度上未知。在这里，我们发现磷脂酰肌醇 4,5-二磷酸 [PI(4,5)P2]（最丰富的质膜磷酸肌醇）的水平随着温度的下降而迅速下降。这种变化触发信号级联传递到胞质二磷酸肌醇磷酸衍生物，其中包括 5-PP-IP4 和 1-IP7，​​这些衍生物对参与肌醇和磷脂 (PL) 代谢的基因发挥调节功能，并抑制蛋白激酶的活性Pho85。与此一致的是，寒冷暴露会触发中性脂质和 PL 变化的特定程序。此外，我们还发现 Pho85 在通过 Ypk1-Orm2 调节电路控制长链碱基 (LCB) 的合成中发挥着关键作用。我们得出的结论是，Pho85 协调脂质代谢途径的协调反应，确保酵母的热适应。