AMPK: Sensing Glucose as well as Cellular Energy Status

Sheng-Cai Lin (Lead / Corresponding author), David Hardie (Lead / Corresponding author)

Research output: Contribution to journalReview article

158 Citations (Scopus)
309 Downloads (Pure)

Abstract

Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation. This nutrient-sensing mechanism activates AMPK but also primes it for further activation if cellular energy status subsequently falls. Glucose sensing at the lysosome, in which AMPK and other components of the activation complex act antagonistically with another key nutrient sensor, mTORC1, may have been one of the ancestral roles of AMPK.

Original languageEnglish
Pages (from-to)299-313
Number of pages15
JournalCell Metabolism
Volume27
Issue number2
Early online date16 Nov 2017
DOIs
Publication statusPublished - 6 Feb 2018

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Keywords

  • AMP-activated protein kinase
  • AMPK
  • Energy sensing
  • Glucose sensing
  • Nutrient sensing
  • Origin of eukaryotes

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