title: Glutathione is essential to preserve nuclear function and cell survival under oxidative stress.
abstract: Glutathione (GSH) is considered the most important redox buffer of the cell. To better characterize its essential function during oxidative stress conditions, we studied the physiological response of H2O2-treated yeast cells containing various amounts of GSH. We showed that the transcriptional response of GSH-depleted cells is severely impaired, despite an efficient nuclear accumulation of the transcription factor Yap1. Moreover, oxidative stress generates high genome instability in GSH-depleted cells, but does not activate the checkpoint kinase Rad53. Surprisingly, scarce amounts of intracellular GSH are sufficient to preserve cell viability under H2O2 treatment. In these cells, oxidative stress still causes the accumulation of oxidized proteins and the inactivation of the translational activity, but nuclear components and activities are protected against oxidative injury. We conclude that the essential role of GSH is to preserve nuclear function, allowing cell survival and growth resumption after oxidative stress release. We propose that cytosolic proteins are part of a protective machinery that shields the nucleus by scavenging reactive oxygen species before they can cross the nuclear membrane.
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Hatem
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Berthonaud
authors.affiliation: CNRS, Institut Curie, UMR3348 "Genotoxic Stress and Cancer," F-91405 Orsay, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Dardalhon
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lagniel
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Baudouin-Cornu
authors.affiliation: CNRS, Institut Curie, UMR3348 "Genotoxic Stress and Cancer," F-91405 Orsay, France.
authors.forename: Meng-Er
authors.initials: ME
authors.lastname: Huang
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Labarre
authors.affiliation: CEA, iBiTecS, F-91191 Gif-sur-Yvette, France; CNRS, FRE3377, F-91191 Gif-sur-Yvette, France; Université Paris-Sud, FRE3377, F-91191 Gif-sur-Yvette, France. Electronic address: stephane.chedin@cea.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chédin
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050296:Microbial Viability; D018384:Oxidative Stress; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D006861:Hydrogen Peroxide; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae; D005978:Glutathione
keywords: Free radicals; GSH; H(2)O(2); Nuclear function; Oxidative stress response; Protein carbonylation; Starvation