title: Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control.
abstract: Glutathione contributes to thiol-redox control and to extra-mitochondrial iron-sulphur cluster (ISC) maturation. To determine the physiological importance of these functions and sort out those that account for the GSH requirement for viability, we performed a comprehensive analysis of yeast cells depleted of or containing toxic levels of GSH. Both conditions triggered an intense iron starvation-like response and impaired the activity of extra-mitochondrial ISC enzymes but did not impact thiol-redox maintenance, except for high glutathione levels that altered oxidative protein folding in the endoplasmic reticulum. While iron partially rescued the ISC maturation and growth defects of GSH-depleted cells, genetic experiments indicated that unlike thioredoxin, glutathione could not support by itself the thiol-redox duties of the cell. We propose that glutathione is essential by its requirement in ISC assembly, but only serves as a thioredoxin backup in cytosolic thiol-redox maintenance. Glutathione-high physiological levels are thus meant to insulate its cytosolic function in iron metabolism from variations of its concentration during redox stresses, a model challenging the traditional view of it as prime actor in thiol-redox control.
authors.affiliation: LSOC, DSV, IBITECS, CEA-Saclay, France.
authors.forename: Chitranshu
authors.initials: C
authors.lastname: Kumar
authors.forename: Aeid
authors.initials: A
authors.lastname: Igbaria
authors.forename: Benoît
authors.initials: B
authors.lastname: D'Autreaux
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Planson
authors.forename: Christophe
authors.initials: C
authors.lastname: Junot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Godat
authors.forename: Anand K
authors.initials: AK
authors.lastname: Bachhawat
authors.forename: Agnès
authors.initials: A
authors.lastname: Delaunay-Moisan
authors.forename: Michel B
authors.initials: MB
authors.lastname: Toledano
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D013438:Sulfhydryl Compounds; D007501:Iron; D005978:Glutathione