New insights into activation and function of the AMPK

Gregory R. Steinberg (Lead / Corresponding author), D Grahame Hardie (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

Abstract

The classical role of AMP-activated protein kinase (AMPK) is as a cellular energy sensor activated by falling energy status, signalled by increases in AMP to ATP and ADP to ATP ratios. Once activated, AMPK acts to restore energy homeostasis by promoting ATP-producing catabolic pathways while inhibiting energy-consuming processes. In this Review, we provide an update on this canonical (AMP/ADP-dependent) activation mechanism, but focus mainly on recently described non-canonical pathways, including those by which AMPK senses the availability of glucose, glycogen or fatty acids and by which it senses damage to lysosomes and nuclear DNA. We also discuss new findings on the regulation of carbohydrate and lipid metabolism, mitochondrial and lysosomal homeostasis, and DNA repair. Finally, we discuss the role of AMPK in cancer, obesity, diabetes, nonalcoholic steatohepatitis (NASH) and other disorders where therapeutic targeting may exert beneficial effects.

Original languageEnglish
Number of pages18
JournalNature Reviews Molecular Cell Biology
Early online date31 Oct 2022
DOIs
Publication statusE-pub ahead of print - 31 Oct 2022

Keywords

  • Cancer
  • Drug discovery
  • Metabolism
  • Nutrient signalling

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