mucidin and funiculosin-(anthraquinone)

Antimycin-resistant (AR) mutants of the yeast Kluyveromyces lactis, obtained either spontaneously or after manganese treatment, were isolated and genetically characterized. Most of the mutants obtained after manganese mutagenesis and two spontaneous mutants, tolerated high antimycin concentrations (more than 10 micrograms/ml) and were extrachromosomal. One mutant which grew only in low antimycin (1 microgram/ml) showed a Mendelian type of inheritance. The extrachromosomal mutants could be assigned to at least two genetic loci (ARI and ARII). Mutants representative of these two groups showed increased resistance to the antibiotic when the respiration of whole cells or mitochondria was studied. Extrachromosomal mutants of Saccharomyces cerevisiae resistant to antimycin were also induced with manganese, isolated and characterized. Comparative studies of the antimycin-resistant mutants of K. lactis and S. cerevisiae permitted the following observations: a) K. lactis is more resistant to antimycin, funiculosin, mucidin and diuron than S. cerevisiae, as are the AR mutants; b) K. lactis shows correlated sensitivity to funiculosin differing in this aspect from S. cerevisiae; c) the antimycin-resistant mutants of K. lactis belonging to group II (ARII) were also resistant to diuron, tolerating concentrations of more than 200 micrograms/ml; d) all extrachromosomal antimycin-resistant-mutants of S. cerevisiae and some of the AR mutants of K. lactis were more sensitive to mucidin than the wild type.

Topics: Alkenes; Anthraquinones; Antifungal Agents; Antimycin A; Diuron; Drug Resistance, Microbial; Fatty Acids, Unsaturated; Genes, Fungal; Kinetics; Kluyveromyces; Meiosis; Methacrylates; Mitochondria; Mitosis; Mutation; Oxygen Consumption; Saccharomycetales; Strobilurins

Changes are described that are brought about by antimycin, NoHOQnO, funiculosin, myxothiazol and mucidin in the alpha-, beta- and gamma-absorption bands of reduced and oxidized cytochromes b in the isolated complex bc1 form beef heart mitochondria. The inhibitors can be divided into 2 groups. Antimycin, funiculosin and NoHOQnO are likely to shift the spectrum of b-562 and compete for specific binding with complex bc1, with each other but not with myxothiazol and mucidin. The spectral effects of the latter two inhibitors are more difficult to interpret and may involve contributions not only from b-562 but from b-566 as well. The existence of 2 independent inhibitor binding-sites in the complex bc1 corroborates the Q-cycle hypothesis.

Topics: Alkenes; Animals; Anthraquinones; Antimycin A; Cattle; Cytochrome b Group; Electron Transport; Electron Transport Complex III; Fatty Acids, Unsaturated; Hydroxyquinolines; Methacrylates; Mitochondria, Heart; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Quinone Reductases; Spectrophotometry; Strobilurins; Thiazoles

Antimycin, 2-nonyl-4-hydroxyquinoline N-oxide and funiculosin induce O.2(-) generation by submitochondrial particles oxidizing succinate, whereas KCN, mucidin, myxothiazol or 2,3-dimercaptopropanol inhibit O.2(-) generation. Thenoyltrifluoroacetone does not induce superoxide production by itself but slightly stimulates the reaction initiated by antimycin. The results indicate that auto-oxidation of unstable ubisemiquinone formed in centre o of the Q-cycle generates most of the O.2(-) radicals in the cytochrome bc1-site of the mitochondrial respiratory chain.

Topics: Alkenes; Animals; Anthraquinones; Antimycin A; Cattle; Dimercaprol; Electron Transport Complex III; Fatty Acids, Unsaturated; Hydroxyquinolines; Methacrylates; Mitochondria, Heart; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Oxygen; Quinone Reductases; Strobilurins; Superoxides; Thenoyltrifluoroacetone; Thiazoles