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AMPK represses TOP mRNA translation but not global protein synthesis in liver

Ali K Reiter1, Douglas R Bolster, Stephen J Crozier

  • 1Department of Cellular and Molecular Physiology, The Pennsylvania State College of Medicine, PO Box 850, Hershey, PA 17033, USA.

Biochemical and Biophysical Research Communications
|July 22, 2008
PubMed

Insights

AMP-activated protein kinase (AMPK) activation in the liver represses translation of specific 5'-terminal oligopyrimidine (TOP) mRNAs. This occurs independently of changes in global protein synthesis or S6K1/rpS6 phosphorylation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • AMP-activated protein kinase (AMPK) inhibits mammalian target of rapamycin complex 1 (mTORC1) signaling.
  • mTORC1 inhibition reduces protein synthesis in muscle but not liver.
  • The specific impact of AMPK on liver mRNA translation requires further elucidation.

Purpose of the Study:

  • To investigate the effects of AMPK activation on mTORC1 signaling and mRNA translation in rat liver.
  • To determine if AMPK activation impacts global protein synthesis or specific mRNA translation in the liver.

Main Methods:

  • Treadmill running was used to activate AMPK in rat liver.
  • Analysis of mTORC1 signaling pathway components (e.g., 4E-BP1, S6K1, rpS6).
  • Measurement of global protein synthesis and translation of specific mRNAs (TOP and non-TOP).

Main Results:

  • AMPK activation repressed the translation of 5"-terminal oligopyrimidine (TOP) mRNAs encoding rpS6, rpS8, and eEF1alpha.
  • Global protein synthesis and translation of GAPDH and beta-actin mRNAs remained unchanged.
  • Basal phosphorylation of 4E-BP1 was reduced, but S6K1 and rpS6 phosphorylation were not significantly affected.

Conclusions:

  • In the liver, AMPK activation selectively represses the translation of TOP mRNAs.
  • This repression occurs via a mechanism independent of reduced S6K1 or rpS6 phosphorylation.
  • AMPK plays a distinct role in regulating protein synthesis in the liver compared to muscle.

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