Glutathione depletion leads to delayed growth stasis in Saccharomyces cerevisiae: evidence of a partially overlapping role for thioredoxin

Disruption of the first enzyme of glutathione biosynthesis in both Saccharo myces cerevisiae and Schizosaccharomyces pombe leads to a glutathione auxot rophy phenotype on plates. However, growth experiments in liquid medium rev ealed that the cessation of growth resulting from glutathione depletion in these yeasts is very delayed in S. cerevisiae compared to S. pombe. Glutath ione metabolism was investigated to understand this delayed growth stasis i n S. cerevisiae. The assimilation of reduced and oxidized glutathione, the intracellular storage pools of glutathione and the turnover of this compoun d were investigated and found to be similar in both yeasts. A possible over lapping role of intracellular thioredoxin in causing delayed stasis was stu died. Yeast thioredoxin was overexpressed in S. cerevisiae and was found to partially relieve the dependence of S. cerevisiae glutathione auxotrophs o n extracellular glutathione in glucose-grown cultures, as well as in glycer ol-grown cultures where conditions of increased glutathione requirements ex ists in the cell. By partially, but not completely, compensating for glutat hione deficiency in this yeast, thioredoxin thus appeared to be the major f actor that was causing the delayed growth stasis following glutathione depl etion in this yeast.