In Schizosaccharomyces pombe, a general strategy for survival in response to environmental changes is sexual differentiation, which is triggered by TORC1 inactivation. However, mechanisms of TORC1 regulation in fission yeast remain poorly understood. In this study, we found that Pef1, which is an ortholog of mammalian CDK5, regulates the initiation of sexual differentiation through positive regulation of TORC1 activity. Conversely, deletion of pef1 leads to activation of autophagy and subsequent excessive TORC1 reactivation during the early phases of the nitrogen starvation response. This excessive TORC1 reactivation results in the silencing of the Ste11-Mei2 pathway and mating defects. Additionally, we found that pef1 genetically interacts with tsc1 and tsc2 for TORC1 regulation, and physically interacts with three cyclins, Clg1, Pas1 and Psl1. The double deletion of clg1 and pas1 promotes activation of autophagy and TORC1 during nitrogen starvation, similar to what is seen in pef1 cells. Overall, our work suggests that Pef1–Clg1 and Pef1–Pas1 complexes regulate initiation of sexual differentiation through control of the TSC–TORC1 pathway and autophagy.

在粟酒裂殖酵母中，响应环境变化的一般生存策略是性分化，这是由 TORC1 失活触发的。然而，人们对裂殖酵母中 TORC1 调控机制仍知之甚少。在这项研究中，我们发现Pef1是哺乳动物CDK5的直系同源物，通过正向调节TORC1活性来调节性分化的启动。相反，删除pef1会导致自噬激活，并随后在氮饥饿反应的早期阶段过度激活 TORC1。TORC1 过度重新激活会导致 Ste11-Mei2 通路沉默和交配缺陷。此外，我们发现pef1在基因上与tsc1和tsc2相互作用以调节 TORC1，并在物理上与三种细胞周期蛋白 Clg1、Pas1 和 Psl1 相互作用。clg1和pas1的双重缺失会在氮饥饿期间促进自噬和 TORC1 的激活，类似于pef1细胞中的情况。总的来说，我们的工作表明 Pef1-Clg1 和 Pef1-Pas1 复合物通过控制 TSC-TORC1 通路和自噬来调节性分化的启动。