AMPK: an energy-sensing pathway with multiple inputs and outputs

By G. Hardie, Bethany E. Schaffer, A. Brunet. Trends in Cell Biology, 2015

809 citations recorded by the source corpus.

Summary The 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, non-canonical 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, which 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.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/330cb2237dbfe25797e93d10f6a4fb64f61ab621

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In Cancer Research

1. Jian‐Kang Zhu
2. Ping Gao
3. Huafeng Zhang
4. Linchong Sun

In Molecular Biology

1. Jian‐Kang Zhu
2. Ping Gao
3. Huafeng Zhang
4. Linchong Sun

Citations in the corpus

• Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “AMPK is a sensor of cellular energy status consistent with the ratios of AMP:ATP and ADP:ATP, and this kinase is activated by an increase in AMP or ADP but inactivated by ATP (Hardie, 2011; Hardie et al., 2016).”
• Metformin promotes antitumor immunity via endoplasmic reticulum-associated degradation of PD-L1 (2018, positive): “Based on the reported phospho-motif of AMPK (Hardie et al., 2016), S195 of PD-L1 was predicted as the phospho-site for AMPK (Figure S2C), which was also detected by mass spectrometric analysis (Table S1).”
• Abiotic stress signaling and responses in plants (2016, background): “SnRKs are related to the yeast SNF1 and mammalian AMPK, which are key sensors of cellular energy status (Hardie et al., 2016).”