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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2044-2056
Number of pages13
JournalEMBO Journal
Issue number10
StatePublished - 18 May 2011
Externally publishedYes


  • glutathione
  • iron-sulphur cluster
  • oxidative protein folding
  • redox homoeostasis
  • thioredoxin

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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