The DOI matches its Crossref record; 256 of the 256 references it cites were found in a registry or an index.
AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control
Open accessAbstract
The AMPK (AMP-activated protein kinase) and TOR (target-of-rapamycin) pathways are interlinked, opposing signaling pathways involved in sensing availability of nutrients and energy and regulation of cell growth. AMPK (Yin, or the "dark side") is switched on by lack of energy or nutrients and inhibits cell growth, while TOR (Yang, or the "bright side") is switched on by nutrient availability and promotes cell growth. Genes encoding the AMPK and TOR complexes are found in almost all eukaryotes, suggesting that these pathways arose very early during eukaryotic evolution. During the development of multicellularity, an additional tier of cell-extrinsic growth control arose that is mediated by growth factors, but these often act by modulating nutrient uptake so that AMPK and TOR remain the underlying regulators of cellular growth control. In this review, we discuss the evolution, structure, and regulation of the AMPK and TOR pathways and the complex mechanisms by which they interact.
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“However, this activation also promotes catabolic pathways, such as mitochondrial biogenesis and autophagy, which can counteract the anabolic processes necessary for muscle hypertrophy induced by resistance training [228].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [228]
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“However, this activation also promotes catabolic pathways, such as mitochondrial biogenesis and autophagy, which can counteract the anabolic processes necessary for muscle hypertrophy induced by resistance training [228].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [228]
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“In hypoxic senescent cells, mTOR activity decrease is mediated by activation of AMP-activated protein kinase (AMPK) that helps to maintain the energy balance under low-oxygen conditions [161,164].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [164]
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Cites
mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
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TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464
Research works printed but not linked: 1
- Ling, 2020, Nat. Metab., mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress, 2, 41
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Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy
Li, Q., Geng, S., Luo, H., Wang, W., Mo, Y.-Q., Luo, Q., Wang, L., Song, G.-B., Sheng, J.-P., & Xu, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01953-7 · Cited by 546
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395
Izquierdo, M., de Souto Barreto, P., Arai, H., Bischoff-Ferrari, H. A., Cadore, E. L., Cesari, M., Chen, L.-K., Coen, P. M., Courneya, K. S., Duque, G., et al. (2025) · The Journal of nutrition, health and aging · doi:10.1016/j.jnha.2024.100401 · Cited by 273
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Metadata
- Authors
- González, A., Hall, M. N., Lin, S.-C., & Hardie, D. G.
- Affiliations
- University of Basel (CH)
- Xiamen University (CN)
- University of Dundee (GB)
- Corresponding author
- Hardie, D. Grahame
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 31
- Issue
- 3
- Pages
- 472-492
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3010443092
- Cited by
- 797
- References
- 256
- Citations by year
- 2026: 119 · 2025: 122 · 2024: 135 · 2023: 129 · 2022: 143 · 2021: 116 · 2020: 31
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc-nd)
- edoc (University of Basel)
- Funders
- Centro de Investigación e Innovación en Energía Marina (609883)
- National Natural Science Foundation of China (31430094, 31690101, 31730058, 31601152)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B-179569)
- European Research Council
- National Key Research and Development Program of China (2016YFA0502001)
- Wellcome Trust (204766)
- Universität Basel
- Louis-Jeantet Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- AMPK, target of rapamycin, nutrient sensing, energy sensing, cell growth regulation, TOR signaling, AMPK signaling, evolution of signaling pathways, eukaryotic evolution, multicellularity, growth factor signaling, nutrient uptake, kinase regulation
- MeSH terms
- Nutrients, Animals, Cells, DNA Damage, Humans, Cell Proliferation, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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