Mechanical stresses, including high hydrostatic pressure, elicit diverse physiological effects on organisms. Gtr1, Gtr2, Ego1 (also known as Meh1) and Ego3 (also known as Slm4), central regulators of the TOR complex 1 (TORC1) nutrient signaling pathway, are required for the growth of Saccharomyces cerevisiae cells under high pressure. Here, we showed that a pressure of 25 MPa (~250 kg/cm²) stimulates TORC1 to promote phosphorylation of Sch9, which depends on the EGO complex (EGOC) and Pib2. Incubation of cells at this pressure aberrantly increased glutamine and alanine levels in the ego1, gtr1, tor1 and pib2 mutants, whereas the polysome profiles were unaffected. Moreover, we found that glutamine levels were reduced by combined deletions of EGO1, GTR1, TOR1 and PIB2 with GLN3. These results suggest that high pressure leads to the intracellular accumulation of amino acids. Subsequently, Pib2 loaded with glutamine stimulates the EGOC–TORC1 complex to inactivate Gln3, downregulating glutamine synthesis. Our findings illustrate the regulatory circuit that maintains intracellular amino acid homeostasis and suggest critical roles for the EGOC–TORC1 and Pib2–TORC1 complexes in the growth of yeast under high hydrostatic pressure.

机械应力，包括高静水压力，会对生物体产生多种生理效应。Gtr1、Gtr2、Ego1（也称为 Meh1）和 Ego3（也称为 Slm4）是 TOR 复合物 1 (TORC1) 营养信号通路的中央调节因子，是酿酒酵母细胞在高压下生长所必需的。^{在这里，我们发现25 MPa (~250 kg/cm 2} )的压力会刺激TORC1促进Sch9的磷酸化，这取决于EGO复合物(EGOC)和Pib2。在此压力下孵育细胞会异常增加ego1、gtr1、tor1和pib2突变体中的谷氨酰胺和丙氨酸水平，而多核糖体谱不受影响。此外，我们发现EGO1、GTR1、TOR1和PIB2与GLN3的联合删除可降低谷氨酰胺水平。这些结果表明高压导致细胞内氨基酸的积累。随后，负载谷氨酰胺的 Pib2 刺激 EGOC-TORC1 复合物使 Gln3 失活，从而下调谷氨酰胺合成。我们的研究结果阐明了维持细胞内氨基酸稳态的调节回路，并表明 EGOC-TORC1 和 Pib2-TORC1 复合物在高静水压下酵母生长中的关键作用。