Multiple drug resistance in the fission yeast Schizosaccharomyces pombe: Correlation between drug and amino acid uptake and membrane ATPase activities.

Cyh3 and cyh4, multiple drug resistant strains of Schizosaccharomyces pombe, show a much reduced uptake of trichodermin, chloramphenicol, cycloheximide, L-lysine, glycine, L-threonine, L-glutamine, L-arginine and L-glutamic acid when compared to wild type. The plasma membrane and mitochondrial ATPase activities of these mutants are also greatly reduced. Since the uptake of such compounds is likely to be driven by a proton electrochemical gradient set up by the membrane ATPase it is suggested that the primary effect of these mutations is at the level of the membrane ATPase. Another drug resistant strain, cyh1, which is resistant only to high levels of cycloheximide, shows increased uptake of trichodermin, L-lysine, glycine, L-threonine, L-glutamine when compared to wild type. The plasma membrane and mitochondrial ATPases of cyh1 are considerably greater than those of wild type. It has been shown previously that cyh1 possesses an altered 60S ribosonal subunit protein when compared to wild type and this makes it resistant to cycloheximide. There is no obvious explanation as to how this change could lead to the alterations in drug and amino acid uptake and in ATPase activities observed.