Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae.

Autor:	Alfatah M; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore. Electronic address: alfatahm@bii.a-star.edu.sg., Cui L; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore 138602, Singapore., Goh CJH; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore., Cheng TYN; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore., Zhang Y; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore., Naaz A; Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore., Wong JH; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore., Lewis J; Institute of Molecular and Cellular Biology, 61 Biopolis Drive, Singapore 138673, Singapore., Poh WJ; Bioinformatics Institute, A(∗)STAR, 30 Biopolis Street, Singapore 138671, Singapore., Arumugam P; Singapore Institute of Food and Biotechnology Innovation, A(∗)STAR, 31 Biopolis Way, Singapore 138669, Singapore; Nanyang Technological University, School of Biological Sciences, Singapore 637551, Singapore. Electronic address: parumugam@sifbi.a-star.edu.sg.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Oct 31; Vol. 42 (10), pp. 113205. Date of Electronic Publication: 2023 Oct 04.
DOI:	10.1016/j.celrep.2023.113205
Abstrakt:	Target of Rapamycin Complex 1 (TORC1) is a conserved eukaryotic protein complex that links the presence of nutrients with cell growth. In Saccharomyces cerevisiae, TORC1 activity is positively regulated by the presence of amino acids and glucose in the medium. However, the mechanisms underlying nutrient-induced TORC1 activation remain poorly understood. By utilizing an in vivo TORC1 activation assay, we demonstrate that differential metabolism of glucose activates TORC1 through three distinct pathways in yeast. The first "canonical Rag guanosine triphosphatase (GTPase)-dependent pathway" requires conversion of glucose to fructose 1,6-bisphosphate, which activates TORC1 via the Rag GTPase heterodimer Gtr1 GTP -Gtr2 GDP . The second "non-canonical Rag GTPase-dependent pathway" requires conversion of glucose to glucose 6-phosphate, which activates TORC1 via a process that involves Gtr1 GTP -Gtr2 GTP  and mitochondrial function. The third "Rag GTPase-independent pathway" requires complete glycolysis and vacuolar ATPase reassembly for TORC1 activation. We have established a roadmap to deconstruct the link between glucose metabolism and TORC1 activation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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