title: The AMPK family member Snf1 protects Saccharomyces cerevisiae cells upon glutathione oxidation.
abstract: The AMPK/Snf1 kinase has a central role in carbon metabolism homeostasis in Saccharomyces cerevisiae. In this study, we show that Snf1 activity, which requires phosphorylation of the Thr210 residue, is needed for protection against selenite toxicity. Such protection involves the Elm1 kinase, which acts upstream of Snf1 to activate it. Basal Snf1 activity is sufficient for the defense against selenite, although Snf1 Thr210 phosphorylation levels become increased at advanced treatment times, probably by inhibition of the Snf1 dephosphorylation function of the Reg1 phosphatase. Contrary to glucose deprivation, Snf1 remains cytosolic during selenite treatment, and the protective function of the kinase does not require its known nuclear effectors. Upon selenite treatment, a null snf1 mutant displays higher levels of oxidized versus reduced glutathione compared to wild type cells, and its hypersensitivity to the agent is rescued by overexpression of the glutathione reductase gene GLR1. In the presence of agents such as diethyl maleate or diamide, which cause alterations in glutathione redox homeostasis by increasing the levels of oxidized glutathione, yeast cells also require Snf1 in an Elm1-dependent manner for growth. These observations demonstrate a role of Snf1 to protect yeast cells in situations where glutathione-dependent redox homeostasis is altered to a more oxidant intracellular environment and associates AMPK to responses against oxidative stress.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pérez-Sampietro
authors.forename: Celia
authors.initials: C
authors.lastname: Casas
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D009154:Mutation; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020887:Selenious Acid / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D013912:Threonine; D011494:Protein Kinases; C411302:ELM1 protein, S cerevisiae; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D020887:Selenious Acid; D005978:Glutathione; D010100:Oxygen