AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance

Mol Cell. 2017 Jun 15;66(6):789-800. doi: 10.1016/j.molcel.2017.05.032.

Abstract

AMPK is a highly conserved master regulator of metabolism, which restores energy balance during metabolic stress both at the cellular and physiological levels. The identification of numerous AMPK targets has helped explain how AMPK restores energy homeostasis. Recent advancements illustrate novel mechanisms of AMPK regulation, including changes in subcellular localization and phosphorylation by non-canonical upstream kinases. Notably, the therapeutic potential of AMPK is widely recognized and heavily pursued for treatment of metabolic diseases such as diabetes, but also obesity, inflammation, and cancer. Moreover, the recently solved crystal structure of AMPK has shed light both into how nucleotides activate AMPK and, importantly, also into the sites bound by small molecule activators, thus providing a path for improved drugs.

Keywords: AMPK; energy restoration; metabolic adaptation; therapeutic activation; trimeric complex.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Autophagy
  • Energy Metabolism* / drug effects
  • Enzyme Activation
  • Enzyme Activators / therapeutic use
  • Humans
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / enzymology
  • Metabolic Diseases / pathology
  • Mitochondria / enzymology
  • Mitochondria / pathology
  • Mitophagy
  • Models, Molecular
  • Phosphorylation
  • Protein Conformation
  • Proteolysis
  • Signal Transduction* / drug effects
  • Structure-Activity Relationship
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Enzyme Activators
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases