Glutathione Reductase/Glutathione Is Responsible for Cytotoxic Elemental Sulfur Tolerance via Polysulfide Shuttle in Fungi

• Published in: The Journal of biological chemistry 2011-06, Vol.286 (23), p.20283-20291
• Main Authors: Sato, Ikuo, Shimatani, Kanami, Fujita, Kensaku, Abe, Tsuyoshi, Shimizu, Motoyuki, Fujii, Tatsuya, Hoshino, Takayuki, Takaya, Naoki
• Format: Article
• Language: English
• Subjects: Aspergillus nidulans - genetics; Aspergillus nidulans - metabolism; Drug Resistance, Fungal - drug effects; Drug Resistance, Fungal - physiology; Electron Transport; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Fusarium - genetics; Fusarium - metabolism; Glutathione; Glutathione - genetics; Glutathione - metabolism; Glutathione Reductase - genetics; Glutathione Reductase - metabolism; Metabolism; Mutation; Oxidation-Reduction - drug effects; Oxidative Stress; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sulfides - metabolism; Sulfur; Sulfur - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.225979

Fungi that can reduce elemental sulfur to sulfide are widely distributed, but the mechanism and physiological significance of the reaction have been poorly characterized. Here, we purified elemental sulfur-reductase (SR) and cloned its gene from the elemental sulfur-reducing fungus Fusarium oxysporum. We found that NADPH-glutathione reductase (GR) reduces elemental sulfur via glutathione as an intermediate. A loss-of-function mutant of the SR/GR gene generated less sulfide from elemental sulfur than the wild-type strain. Its growth was hypersensitive to elemental sulfur, and it accumulated higher levels of oxidized glutathione, indicating that the GR/glutathione system confers tolerance to cytotoxic elemental sulfur by reducing it to less harmful sulfide. The SR/GR reduced polysulfide as efficiently as elemental sulfur, which implies that soluble polysulfide shuttles reducing equivalents to exocellular insoluble elemental sulfur and generates sulfide. The ubiquitous distribution of the GR/glutathione system together with our findings that GR-deficient mutants derived from Saccharomyces cerevisiae and Aspergillus nidulans reduced less sulfur and that their growth was hypersensitive to elemental sulfur indicated a wide distribution of the system among fungi. These results indicate a novel biological function of the GR/glutathione system in elemental sulfur reduction, which is distinguishable from bacterial and archaeal mechanisms of glutathione- independent sulfur reduction.