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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/173930 |
| _version_ | 1811696671905546240 |
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| 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 |
| 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 |
| author_sort | Alfatah, Mohammad |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T07:43:05Z |
| format | Journal Article |
| id | ntu-10356/173930 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:43:05Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-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 |
| 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 |
| title | 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_short | Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae |
| title_sort | metabolism of glucose activates torc1 through multiple mechanisms in saccharomyces cerevisiae |
| topic | Medicine, Health and Life Sciences Glucose signaling Glycolysis |
| url | https://hdl.handle.net/10356/173930 |
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