Reduced plasma membrane permeability in a multiple cross-resistant strain of Saccharomyces cerevisiae.
Single nuclear gene inheritance was shown to be responsible for increased resistance to: eight diverse inhibitors of mitochondrial function (antimycin, carbonylcyanide-m-chlorophenylhydrazone, chloramphenicol, oligomycin, tetracycline, triethyltin bromide, triphenylmethylphosphonium bromide and triton-X-165); and an inhibitor of cytoplasmic protein synthesis (cycloheximide). Continuous monitoring of oxygen uptake during respiratory adaptation showed that anerobic pretreatment of resistant cells sensitized respiratory adaptation to chloramphenicol and antimycin. However, since a depression of mitochondrial function by catabolite repression did not result in sensitization to antimycin, alteration of the mitochondrial membrane does not appear to be responsible for resistance to mitochondrial inhibition. Alteration of cellular binding sites was not responsible for resistance since in vitro mitochondrial protein synthesis was sensitive to chloramphenicol and in vitro mitochondrial respiration was sensitive to oligomycin, carbonylcyanide-m-chlorophenylhydrazone, and antimycin. Autoradiography of an ethylacetate-ethanol extract of [14C]chloramphenicol-treated resistant cells indicated that resistance was not due to enzymatic modification of inhibitors. The maintenance of an antimycin-resistant respiration by protoplasts of resistant cells ruled out the involvement of the cell wall in cellular resistance. The reduced transport of [14C]chloramphenicol by resistant cells (1% of normal cells) indicated that a single nuclear gene mutation can alter the permeability of the plasma membrane to many diverse inhibitors.
D000693:Anaerobiosis; D000968:Antimycin A / Q000494:pharmacology; D001345:Autoradiography; D002250:Carbon Radioisotopes; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002473:Cell Wall / Q000187:drug effects; D002701:Chloramphenicol / Q000378:metabolism / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005656:Fungal Proteins / Q000096:biosynthesis; D005796:Genes; D005947:Glucose / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption; D011523:Protoplasts / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D002250:Carbon Radioisotopes; D005656:Fungal Proteins; D009840:Oligomycins; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000968:Antimycin A; D002701:Chloramphenicol; D005947:Glucose