Regulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses

Rui Fujii; Rai Katsukawa; Eigo Takeda; Eisuke Itakura; Akira Matsuura

doi:10.1016/j.isci.2024.111573

Regulatory dynamics of Sch9 in response to cytosolic acidification: From spatial reconfiguration to cellular adaptation to stresses

iScience. 2024 Dec 10;28(1):111573. doi: 10.1016/j.isci.2024.111573. eCollection 2025 Jan 17.

Authors

Rui Fujii¹, Rai Katsukawa², Eigo Takeda³, Eisuke Itakura⁴, Akira Matsuura⁴

Affiliations

¹ Department of Biology, Graduate School of Science and Engineering, Chiba University, Chiba 263-8522, Japan.
² Department of Biology, Faculty of Science, Chiba University, Chiba 263-8522, Japan.
³ Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
⁴ Department of Biology, Graduate School of Science, Chiba University, Chiba 263-8522, Japan.

Abstract

The regulation of cellular metabolism is crucial for cell survival, with Sch9 in Saccharomyces cerevisiae serving a key role as a substrate of TORC1. Sch9 localizes to the vacuolar membrane through binding to PI(3,5)P₂, which is necessary for TORC1-dependent phosphorylation. This study demonstrates that cytosolic pH regulates Sch9 localization. Under stress conditions that induce cytosolic acidification, Sch9 detached from the vacuolar membrane. In vitro experiments confirmed that Sch9's affinity for PI(3,5)P₂ is pH-dependent. This pH-dependent localization switch is essential for regulating the TORC1-Sch9 pathway. Impairment of the dissociation of Sch9 from the vacuolar membrane in response to cytosolic acidification resulted in the deficient induction of stress response gene expression and delayed the adaptive response to acetic acid stress. These findings indicate the importance of proper Sch9 localization for metabolic reprogramming and stress response in yeast cells.

Keywords: Cell biology; Cellular physiology; Functional aspects of cell biology.