MENADIONE TOXICITY IN SACCHAROMYCES-CEREVISIAE CELLS - ACTIVATION BY CONJUGATION WITH GLUTATHIONE

Menadione (2-methyl-1,4-naphthoquinone) has been used extensively as a n oxidant stressor at the cellular level. However, the mechanism of cy totoxicity of this compound still remains controversial. This study de als with the role of intracellular glutathione in the resistance of th e yeast Saccharomyces cerevisiae to menadione. Incubation with 0.5 mM menadione resulted in a decrease of total glutathione concentration in yeast cells, intracellular formation of menadione S-glutathione conju gate and export of the conjugate from cells. GSH-deficient mutants sho wed lower stimulation of superoxide and hydrogen peroxide production u pon exposure to menadione and were more resistant to menadione than wi ld-type isogenic strains. These results indicate that in yeast cells t he formation of S-glutathione conjugate is a major pathway of menadion e metabolism and that this reaction leads to redox activation of menad ione but permits its removal from the cells.