AMPK: positive and negative regulation, and its role in whole-body energy homeostasis

Curr Opin Cell Biol. 2015 Apr;33:1-7. doi: 10.1016/j.ceb.2014.09.004. Epub 2014 Sep 26.

Abstract

The AMP-activated protein kinase (AMPK) is a sensor of energy status that, when activated by metabolic stress, maintains cellular energy homeostasis by switching on catabolic pathways and switching off ATP-consuming processes. Recent results suggest that activation of AMPK by the upstream kinase LKB1 in response to nutrient lack occurs at the surface of the lysosome. AMPK is also crucial in regulation of whole body energy balance, particularly by mediating effects of hormones acting on the hypothalamus. Recent crystal structures of complete AMPK heterotrimers have illuminated its complex mechanisms of activation, involving both allosteric activation and increased net phosphorylation mediated by effects on phosphorylation and dephosphorylation. Finally, AMPK is negatively regulated by phosphorylation of the 'ST loop' within the catalytic subunit.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Energy Metabolism*
  • Enzyme Activation / drug effects
  • Homeostasis*
  • Humans
  • Hypothalamus / metabolism
  • Lysosomes / metabolism
  • Models, Molecular
  • Protein-Serine-Threonine Kinases / metabolism

Substances

  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases