Molecular and Cellular Biochemistry

, Volume 335, Issue 1–2, pp 91–105

The regulation of AMPK signaling in a natural state of profound metabolic rate depression

  • Christopher J. Ramnanan
  • David C. McMullen
  • Amy G. Groom
  • Kenneth B. Storey
Article
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Abstract

In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK is activated in a model system (desert snail Otala lactea) during a physiological state of profound metabolic rate depression (estivation) in the absence of a rise in AMP. Kinetic characterization indicated a strong increase in AMPK activity and phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an established regulator of AMPK. Accordingly, ~2-fold increases in AMPKα1 protein and activity were observed with LKB1 immunoprecipitates from estivating snails. In vitro studies determined that AMPK in crude extracts was activated in the presence of cGMP and deactivated in conditions that permitted protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKα1 protein and activity increased in PKG immunoprecipitates from estivating tissues, suggesting a novel role for PKG in the regulation of AMPK in vivo. We evaluated several downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly inhibited in estivation, consistent with increased P-Ser79 content, and in vitro stimulation of AMPK negated citrate’s ability to stimulate ACC aggregation. Analysis of other targets revealed a strong decrease in PPARγ-coactivator 1α expression in both tissues, which was related to decreased gluconeogenic protein expression in hepatic tissue, but no changes in mitochondrial biogenesis markers in muscle. We concluded that AMPK activation in O. lactea aids in facilitating the suppression of anabolic pathways, without necessarily activating ATP-generating catabolism.

Keywords

AMP-activated protein kinase Acetyl-CoA carboxylase Gluconeogenesis Mitochondrial biogenesis Metabolic rate depression Estivation 

Abbreviations

AMPK

AMP-activated protein kinase

ACC

Acetyl-CoA carboxylase

PGC1α

PPARγ-coactivator 1α

PKG

Protein kinase G

PP2A

Protein phosphatase type-2A

G6Pase

Glucose-6-phosphatase

PEPCK

Phosphoenolpyruvate carboxykinase

NRF1

Nuclear respiratory factor 1

mtTFA

Mitochondrial transcription factor A

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Christopher J. Ramnanan
    • 1
  • David C. McMullen
    • 2
  • Amy G. Groom
    • 2
  • Kenneth B. Storey
    • 2
  1. 1.Department of Molecular PhysiologyVanderbilt University School of MedicineNashvilleUSA
  2. 2.Institute of Biochemistry and Department of BiologyCarleton UniversityOttawaCanada

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