Glutathione S-transferases interact with AMP-activated protein kinase: evidence for S-glutathionylation and activation in vitro

Anna Klaus; Sarah Zorman; Alexandre Berthier; Cécile Polge; Sacnicte Ramirez; Sylvie Michelland; Michel Sève; Didier Vertommen; Mark Rider; Nicolas Lentze; Daniel Auerbach; Uwe Schlattner

doi:10.1371/journal.pone.0062497

Glutathione S-transferases interact with AMP-activated protein kinase: evidence for S-glutathionylation and activation in vitro

PLoS One. 2013 May 31;8(5):e62497. doi: 10.1371/journal.pone.0062497. Print 2013.

Authors

Anna Klaus¹, Sarah Zorman, Alexandre Berthier, Cécile Polge, Sacnicte Ramirez, Sylvie Michelland, Michel Sève, Didier Vertommen, Mark Rider, Nicolas Lentze, Daniel Auerbach, Uwe Schlattner

Affiliation

¹ Université Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France.

Abstract

AMP-activated protein kinase (AMPK) is a cellular and whole body energy sensor with manifold functions in regulating energy homeostasis, cell morphology and proliferation in health and disease. Here we apply multiple, complementary in vitro and in vivo interaction assays to identify several isoforms of glutathione S-transferase (GST) as direct AMPK binding partners: Pi-family member rat GSTP1 and Mu-family members rat GSTM1, as well as Schistosoma japonicum GST. GST/AMPK interaction is direct and involves the N-terminal domain of the AMPK β-subunit. Complex formation of the mammalian GSTP1 and -M1 with AMPK leads to their enzymatic activation and in turn facilitates glutathionylation and activation of AMPK in vitro. GST-facilitated S-glutathionylation of AMPK may be involved in rapid, full activation of the kinase under mildly oxidative physiological conditions.

Publication types

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

MeSH terms

AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism*
Animals
Binding Sites
Energy Metabolism / genetics*
Enzyme Activation
Gene Expression
Glutathione / metabolism*
Glutathione Transferase / genetics
Glutathione Transferase / metabolism*
Helminth Proteins / genetics
Helminth Proteins / metabolism*
Humans
Isoenzymes / genetics
Isoenzymes / metabolism
Liver / chemistry
Liver / enzymology
Oxidation-Reduction
Oxidative Stress
Protein Binding
Protein Structure, Tertiary
Protein Subunits / genetics
Protein Subunits / metabolism*
Rats
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Schistosoma japonicum / chemistry
Schistosoma japonicum / enzymology
Signal Transduction

Substances

Helminth Proteins
Isoenzymes
Protein Subunits
Recombinant Proteins
Glutathione Transferase
glutathione S-transferase M1
AMP-Activated Protein Kinases
Glutathione

Grants and funding

This work was supported by EU FP6 contract LSHM-CT-2004-005272 (EXGENESIS), the Fondation pour la Recherche Médicale (given to A.K.) and the French Agence Nationale de Recherche (“chaire d'excellence” given to U.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.