Cells dynamically adapt organelle size to current physiological demand. Organelle growth requires membrane biogenesis and therefore needs to be coordinated with lipid metabolism. The endoplasmic reticulum (ER) can undergo massive expansion, but the underlying regulatory mechanisms are largely unclear. Here, we describe a genetic screen for factors involved in ER membrane expansion in budding yeast and identify the ER transmembrane protein Ice2 as a strong hit. We show that Ice2 promotes ER membrane biogenesis by opposing the phosphatidic acid phosphatase Pah1, called lipin in metazoa. Specifically, Ice2 inhibits the conserved Nem1-Spo7 complex and thus suppresses the dephosphorylation and activation of Pah1. Furthermore, Ice2 cooperates with the transcriptional regulation of lipid synthesis genes and helps to maintain cell homeostasis during ER stress. These findings establish the control of the lipin phosphatase complex as an important mechanism for regulating ER membrane biogenesis.

中文翻译：

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Ice2通过抑制保守的脂质磷酸酶复合物促进酵母中的ER膜生物发生

细胞根据当前的生理需求动态调整细胞器大小。细胞器生长需要膜生物发生，因此需要与脂质代谢相协调。内质网 (ER) 可以进行大规模扩张，但潜在的调节机制在很大程度上尚不清楚。在这里，我们描述了出芽酵母中涉及 ER 膜扩张的因素的遗传筛选，并将 ER 跨膜蛋白 Ice2 确定为一个强大的打击。我们表明 Ice2 通过对抗后生动物中称为 lipin 的磷脂酸磷酸酶 Pah1 来促进 ER 膜生物发生。具体而言，Ice2 抑制保守的 Nem1-Spo7 复合物，从而抑制 Pah1 的去磷酸化和激活。此外，Ice2 与脂质合成基因的转录调控合作，帮助维持内质网应激期间的细胞稳态。这些发现将脂质磷酸酶复合物的控制确立为调节 ER 膜生物发生的重要机制。