Glutathione metabolism and heavy metal detoxification in Schizosaccharomyces pombe

Abstract

Sixty glutathione-deficient mutants (gsh−) of Schizosaccharomyces pombe have been isolated by their resistance towards the mutagen N-methyl-N{\textasciiacutex}-nitro-N-nitrosoguanidine (MNNG) and their sensitivity to the heavy metal Cadmium (Cd). fifty-three mutants show glutathione contents of less than 5{%} compared with the wild-type. The residual glutathione contents correlate with the resistance to MNNG, with the sensitivity to Cd and with the growth rate in minimal medium. The gsh−, Cd-sensitive (Cds) mutants also show sensitivity to other heavy metals. Wild-type strains, but not the gsh− mutants, are able to excrete the heavy metal, very likely as a sulfide-containing compound. This inability of the mutants to excrete Cd and other heavy metals causes an increase in Cd accumulation in the gsh− mutants versus the wild-type. In 60{%} of the mutants the glutathione deficiency is very likely due to a deficiency in the enzyme glutathione synthetase (GS), the other 40{%} appear to be deficient in gamma-glutamyl-cysteine synthetase (GCS).