The yeast copper/zinc superoxide dismutase and the pentose phosphate pathway play overlapping roles in oxidative stress protection.
In Saccharomyces cerevisiae, loss of cytosolic superoxide dismutase (Sod1) results in several air-dependent mutant phenotypes, including methionine auxotrophy and oxygen sensitivity. Here we report that these two sod1Delta phenotypes were specifically suppressed by elevated expression of the TKL1 gene, encoding transketolase of the pentose phosphate pathway. The apparent connection between Sod1 and the pentose phosphate pathway prompted an investigation of mutants defective in glucose-6-phosphate dehydrogenase (Zwf1), which catalyzes the rate-limiting NADPH-producing step of this pathway. We confirmed that zwf1Delta mutants are methionine auxotrophs and report that they also are oxygen-sensitive. We determined that a functional ZWF1 gene product was required for TKL1 to suppress sod1Delta, leading us to propose that increased flux through the oxidative reactions of the pentose phosphate pathway can rescue sod1 methionine auxotrophy. To better understand this methionine growth requirement, we examined the sulfur compound requirements of sod1Delta and zwf1Delta mutants, and noted that these mutants exhibit the same apparent defect in sulfur assimilation. Our studies suggest that this defect results from the impaired redox status of aerobically grown sod1 and zwf1 mutants, implicating Sod1 and the pentose phosphate pathway as being critical for maintenance of the cellular redox state.
Division of Toxicological Sciences, Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
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Slekar
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Kosman
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Culotta
D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013455:Sulfur / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014174:Transketolase / Q000235:genetics
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D013455:Sulfur; D013482:Superoxide Dismutase; C084088:TKL1 protein, S cerevisiae; D014174:Transketolase