title: Altered intracellular calcium homeostasis and endoplasmic reticulum redox state in Saccharomyces cerevisiae cells lacking Grx6 glutaredoxin.
abstract: Glutaredoxin 6 (Grx6) of Saccharomyces cerevisiae is an integral thiol oxidoreductase protein of the endoplasmic reticulum/Golgi vesicles. Its absence alters the redox equilibrium of the reticulum lumen toward a more oxidized state, thus compensating the defects in protein folding/secretion and cell growth caused by low levels of the oxidase Ero1. In addition, null mutants in GRX6 display a more intense unfolded protein response than wild-type cells upon treatment with inducers of this pathway. These observations support a role of Grx6 in regulating the glutathionylation of thiols of endoplasmic reticulum/Golgi target proteins and consequently the equilibrium between reduced and oxidized glutathione in the lumen of these compartments. A specific function influenced by Grx6 activity is the homeostasis of intracellular calcium. Grx6-deficient mutants have reduced levels of calcium in the ER lumen, whereas accumulation occurs at the cytosol from extracellular sources. This results in permanent activation of the calcineurin-dependent pathway in these cells. Some but not all the phenotypes of the mutant are coincident with those of mutants deficient in intracellular calcium transporters, such as the Golgi Pmr1 protein. The results presented in this study provide evidence for redox regulation of calcium homeostasis in yeast cells.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198 Lleida, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Puigpinós
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198 Lleida, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Casas
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198 Lleida, Spain enric.herrero@cmb.udl.cat.
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis; D017136:Ion Transport; D010084:Oxidation-Reduction; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; C527470:Grx6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013438:Sulfhydryl Compounds; D002118:Calcium