Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae

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 nutr...

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Main Authors: Alfatah, Mohammad, Cui, Liang, Goh, Corinna Jie Hui, Cheng, Trishia Yi Ning, Zhang, Yizhong, Naaz, Arshia, Wong, Jin Huei, Lewis, Jacqueline, Poh, Wei Jie, Arumugam, Prakash
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/173930
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1739302024-03-11T15:32:34Z Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae Alfatah, Mohammad Cui, Liang Goh, Corinna Jie Hui Cheng, Trishia Yi Ning Zhang, Yizhong Naaz, Arshia Wong, Jin Huei Lewis, Jacqueline Poh, Wei Jie Arumugam, Prakash School of Biological Sciences Singapore Institute of Food and Biotechnology Innovation Medicine, Health and Life Sciences Glucose signaling Glycolysis 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 Gtr1GTP-Gtr2GDP. The second "non-canonical Rag GTPase-dependent pathway" requires conversion of glucose to glucose 6-phosphate, which activates TORC1 via a process that involves Gtr1GTP-Gtr2GTP 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. Agency for Science, Technology and Research (A*STAR) Published version We would like to acknowledge A*STAR (Singapore)’s core funding provided to the Arumugam laboratory and A*STAR (Singapore)’s Career Development Fund (C210112008) to the Alfatah laboratory. 2024-03-06T08:21:19Z 2024-03-06T08:21:19Z 2023 Journal Article Alfatah, M., Cui, L., Goh, C. J. H., Cheng, T. Y. N., Zhang, Y., Naaz, A., Wong, J. H., Lewis, J., Poh, W. J. & Arumugam, P. (2023). Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae. Cell Reports, 42(10), 113205-. https://dx.doi.org/10.1016/j.celrep.2023.113205 2211-1247 https://hdl.handle.net/10356/173930 10.1016/j.celrep.2023.113205 37792530 2-s2.0-85172889985 10 42 113205 en Cell Reports © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Glucose signaling
Glycolysis
spellingShingle Medicine, Health and Life Sciences
Glucose signaling
Glycolysis
Alfatah, Mohammad
Cui, Liang
Goh, Corinna Jie Hui
Cheng, Trishia Yi Ning
Zhang, Yizhong
Naaz, Arshia
Wong, Jin Huei
Lewis, Jacqueline
Poh, Wei Jie
Arumugam, Prakash
Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
description 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 Gtr1GTP-Gtr2GDP. The second "non-canonical Rag GTPase-dependent pathway" requires conversion of glucose to glucose 6-phosphate, which activates TORC1 via a process that involves Gtr1GTP-Gtr2GTP 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Alfatah, Mohammad
Cui, Liang
Goh, Corinna Jie Hui
Cheng, Trishia Yi Ning
Zhang, Yizhong
Naaz, Arshia
Wong, Jin Huei
Lewis, Jacqueline
Poh, Wei Jie
Arumugam, Prakash
format Article
author Alfatah, Mohammad
Cui, Liang
Goh, Corinna Jie Hui
Cheng, Trishia Yi Ning
Zhang, Yizhong
Naaz, Arshia
Wong, Jin Huei
Lewis, Jacqueline
Poh, Wei Jie
Arumugam, Prakash
author_sort Alfatah, Mohammad
title Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
title_short Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
title_full Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
title_fullStr Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
title_full_unstemmed Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae
title_sort metabolism of glucose activates torc1 through multiple mechanisms in saccharomyces cerevisiae
publishDate 2024
url https://hdl.handle.net/10356/173930
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