The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs
Open accessAbstract
AMP-activated protein kinase (AMPK) is a key regulator of energy balance expressed ubiquitously in eukaryotic cells. Here we review the canonical adenine nucleotide-dependent mechanism that activates AMPK when cellular energy status is compromised, as well as other, noncanonical activation mechanisms. Once activated, AMPK acts to restore energy homeostasis by promoting catabolic pathways, resulting in ATP generation, and inhibiting anabolic pathways that consume ATP. We also review the various hypothesis-driven and unbiased approaches that have been used to identify AMPK substrates and have revealed substrates involved in both metabolic and non-metabolic processes. We particularly focus on methods for identifying the AMPK target recognition motif and how it can be used to predict new substrates.
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“AMPK is a heterotrimeric serine/threonine kinase composed of a catalytic α subunit (PRKAA1), which is essential for AMPK function through phosphorylation of its activation loop, and regulatory β and γ subunits [12].”
From AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma (2021) · cites this paper as [12]
Experimental — accuracy not yet measuredIn the citing paper
“Aerobic exercise activates AMPK, particularly under low energy availability conditions, as it restores energy balance by increasing glucose uptake and fatty acid oxidation [226,227].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [227]
In the citing paper
“Aerobic exercise activates AMPK, particularly under low energy availability conditions, as it restores energy balance by increasing glucose uptake and fatty acid oxidation [226,227].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [227]
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Cites
WebLogo: A Sequence Logo Generator: Figure 1Preprint
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Resveratrol improves health and survival of mice on a high-calorie diet
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FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
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
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
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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
Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs
Obenauer, J. C. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg584 · Cited by 1,609
The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
Yaffe, M. B., Rittinger, K., Volinia, S., Caron, P. R., Aitken, A., Leffers, H. C. B., Gamblin, S. J., Smerdon, S. J., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)80487-0 · Cited by 1,604
Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
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Cited by
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Abiotic Stress Signaling and Responses in Plants
Zhu, J. (2016) · Cell · doi:10.1016/j.cell.2016.08.029 · Cited by 5,837
AMPK: guardian of metabolism and mitochondrial homeostasis
Herzig, S., & Shaw, R. J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.95 · Cited by 4,192
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance
Garcia, D., & Shaw, R. J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.032 · Cited by 2,061
AMPK: Sensing Glucose as well as Cellular Energy Status
Lin, S., & Hardie, D. G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.009 · Cited by 1,198
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Metadata
- Authors
- Hardie, D. G., Schaffer, B. E., & Brunet, A.
- Affiliations
- University of Dundee (GB)
- Stanford University (US)
- Corresponding author
- Hardie, D. Grahame
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 26
- Issue
- 3
- Pages
- 190-201
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC5881568
- OpenAlex
- W2174118934
- Cited by
- 859
- References
- 75
- Citations by year
- 2026: 41 · 2025: 62 · 2024: 80 · 2023: 69 · 2022: 89 · 2021: 112 · 2020: 97 · 2019: 77 · 2018: 103 · 2017: 80 · 2016: 46
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Cell Biology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (097726)
- Cancer Research UK (C37030/A15101)
- CIRM (RB4-06087)
- NIH (R01 AG031198, T32 CA09302)
- NSF GRFP
- Robert M. and Anne T. Bass Stanford Graduate Fellowship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- AMPK, AMPK activation, energy homeostasis, catabolic pathways, ATP production, substrate recognition motif, substrate prediction
- MeSH terms
- Allosteric Regulation, Amino Acid Sequence, Animals, Energy Metabolism, Enzyme Activation, Humans, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Catalytic Domain, AMP-Activated Protein Kinases
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