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Oxidoreductase enzymes in the vacuole of the yeast Saccharomyces cerevisiae?: Study of glutaredoxins 6 and 7

par Deschamps, Alexandre
Président du jury Van Melderen, Laurence
Promoteur André, Bruno
Publication Non publié, 2024-08-28

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Résumé :

The mechanisms maintaining redox homeostasis in the lysosome and its yeast counterpart, the vacuole, are likely crucial for cell physiology and aging but remain poorly understood. For example, oxidative stress within the lysosome can potentially damage membrane lipids and proteins, leading to membrane permeabilization and cell death. We hypothesized that vacuolar redox balance is primarily maintained by transporters regulating the concentrations of redoxactive compounds inside the vacuole. Supporting this, our recent findings indicate a significant increase in intravacuolar glutathione concentration under more oxidative conditions. Exploitation of the reducing power of glutathione generally requires oxidoreductases, typically from the glutaredoxin subfamily. However, no such enzyme has yet been characterized in the yeast vacuole.This study focuses on two yeast glutaredoxins, Grx6 and Grx7, previously reported to be localized in the early secretory pathway. However, our observations suggest that these enzymes are localized in the vacuole. Moreover, their expression appears particularly high under more oxidative conditions. Initial results regarding their trafficking to the vacuolar lumen point to sorting via the multivesicular body (MVB) pathway. Finally, our findings suggest a role for Grx6 and Grx7 in vacuolar redox homeostasis.