Abstract
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 language | American English |
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Pages (from-to) | 2044-2056 |
Number of pages | 13 |
Journal | EMBO Journal |
Volume | 30 |
Issue number | 10 |
DOIs | |
State | Published - 18 May 2011 |
Externally published | Yes |
Keywords
- glutathione
- iron-sulphur cluster
- oxidative protein folding
- redox homoeostasis
- thioredoxin
All Science Journal Classification (ASJC) codes
- General Immunology and Microbiology
- General Biochemistry,Genetics and Molecular Biology
- Molecular Biology
- General Neuroscience