Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the up-regulation of autophagy and vacuole proteins involved in recycling but also result in the down-regulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Down-regulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.

中文翻译：

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TORC1 通过泛素和 ESCRT 依赖性微自噬调节液泡膜组成

细胞对营养限制的适应需要诱导自噬和溶酶体生物发生，以实现大分子的有效回收。在这里，我们发现饥饿和TORC1失活不仅导致自噬和参与回收的液泡蛋白上调，而且还导致许多液泡膜蛋白下调，以作为液泡重塑过程的一部分提供氨基酸。液泡膜蛋白的下调是通过泛素化启动的，泛素化是通过多种 E3 泛素连接酶（包括 Rsp5、Dsc 复合物和新表征的 E3 连接酶 Pib1）的协调来完成的。Dsc 复合物通过 Rim15-Ume6 信号级联受到 TORC1 的负调节。泛素化后，液泡膜蛋白被分选到管腔中，通过 ESCRT 依赖性微自噬进行降解。因此，我们的研究揭示了 TORC1 失活和液泡生物发生之间的复杂关系。