Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology

Yuichi Morozumi; Fontip Mahayot; Yukiko Nakase; Jia Xin Soong; Sayaka Yamawaki; Fajar Sofyantoro; Yuki Imabata; Arisa H Oda; Miki Tamura; Shunsuke Kofuji; Yutaka Akikusa; Ayu Shibatani; Kunihiro Ohta; Kazuhiro Shiozaki

doi:10.1016/j.isci.2023.108777

Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology

iScience. 2023 Dec 26;27(1):108777. doi: 10.1016/j.isci.2023.108777. eCollection 2024 Jan 19.

Authors

Affiliations

¹ Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
² Faculty of Biology, Universitas Gadjah Mada, Sleman, Yogyakarta 55281, Indonesia.
³ Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
⁴ Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA 95616, USA.

Abstract

Cells cease to proliferate above their growth-permissible temperatures, a ubiquitous phenomenon generally attributed to heat damage to cellular macromolecules. We here report that, in the presence of rapamycin, a potent inhibitor of Target of Rapamycin Complex 1 (TORC1), the fission yeast Schizosaccharomyces pombe can proliferate at high temperatures that usually arrest its growth. Consistently, mutations to the TORC1 subunit RAPTOR/Mip1 and the TORC1 substrate Sck1 significantly improve cellular heat resistance, suggesting that TORC1 restricts fission yeast growth at high temperatures. Aiming for a more comprehensive understanding of the negative regulation of high-temperature growth, we conducted genome-wide screens, which identified additional factors that suppress cell proliferation at high temperatures. Among them is Mks1, which is phosphorylated in a TORC1-dependent manner, forms a complex with the 14-3-3 protein Rad24, and suppresses the high-temperature growth independently of Sck1. Our study has uncovered unexpected mechanisms of growth restraint even below the temperatures deleterious to cell physiology.

Keywords: Biological sciences; Microbial physiology; Microbiology; Molecular microbiology.