Glutathione revisited: A vital function in iron metabolism and ancillary role in thiol-redox control

Chitranshu Kumar, Aeid Igbaria, Benoît D'Autreaux, Anne Gaëlle Planson, Christophe Junot, Emmanuel Godat, Anand K. Bachhawat, Agnés Delaunay-Moisan, Michel B. Toledano

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

Glutathione contributes to thiol-redox control and to extra-mitochondrial irong-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.

שפה מקוריתאנגלית אמריקאית
עמודים (מ-עד)2044-2056
מספר עמודים13
כתב עתEMBO Journal
כרך30
מספר גיליון10
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 18 מאי 2011
פורסם באופן חיצוניכן

ASJC Scopus subject areas

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