Cited by 860Metabolism, Diabetes, and CancerBiochemical and Molecular ResearchPI3K/AKT/mTOR signaling in cancer

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AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs

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Hardie, D. Grahame, Schaffer, Bethany E., Brunet, Anne·2016·Trends in Cell Biology

DOI 10.1016/j.tcb.2015.10.013PMC PMC5881568

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Abstract

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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Authors: Hardie, D. G., Schaffer, B. E., & Brunet, A.
Affiliations: University of Dundee (GB)
Stanford University (US)
Corresponding author: Hardie, D. Grahame
ORCID: Hardie, D. Grahame
Brunet, Anne
Venue: Trends in Cell Biology
Publisher: Elsevier BV
Published: 2016-03
Volume: 26
Issue: 3
Pages: 190-201
ISSN: 0962-8924 (ISSN-L)
DOI: 10.1016/j.tcb.2015.10.013
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (am, 353 d)
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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AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs

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