Isolation and characterization of an uncoupler-resistant mutant of Saccharomyces cerevisiae

Summary One mutant resistant to carbonylcyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, was isolated in Saccharomyces cerevisiae.Genetic analysis showed that a single nuclear gene is responsible for increased resistance; this gene was dominant.The mutant showed cross-resistance or collateral sensitivity to several chemically-unrelated inhibitors (cycloheximide, dinitrophenol, tributhyltin chloride, chloramphenicol).The resistance of the mutant is related to a decreased uptake of CCCP which is not expressed in glucose-starved cells. It was shown that glucose induced a CCCP efflux which was more efficient in the mutant than in the wild-type cells. This effect was correlated to a greater acidification of the internal pH by glucose addition in the mutant cells.It was proposed that resistance was not due to a change of permeability of the plasmic membrane itself but to the change of internal pH which determines the extent of accumulation of weak acids or bases.Abbreviations CCCP carbonylcyanide m-chlorophenylhydrazone - FDA fluoresceine diacetate - EGTA ethyleneglycol-bis((-aminoethyl ether) N,N,N,N-tetraacetic acid - DES diethylstilbestrol