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EMBO J. 2011 May 18;30(10):2044-56. doi: 10.1038/emboj.2011.105. Epub 2011 Apr 8.

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

Author information

  • 1LSOC, DSV, IBITECS, CEA-Saclay, France.

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.

PMID:
21478822
[PubMed - indexed for MEDLINE]
PMCID:
PMC3098478
Free PMC Article

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