Studies on Energy‐Linked Reactions

A series of 62 mutants of Saccharomyces cerevisiae showing high levels of resistance to oligomycin and rutamycin have been isolated. These mutants can be subdivided into two classes on the basis of their cross resistance to a variety of inhibitors and uncouplers of mitochondrial energy‐conservation reactions. Class I mutants show cross resistance to aurovertin, triethyltin, ‘1799’ (a hexafluorotriacetone derivative), uncoupling agents and inhibitors of mitochondrial protein synthesis such as chloramphenicol, mikamycin and spiramycin. Class II mutants are specifically resistant to oligomycin and rutamycin and show no cross resistance to aurovertin, triethyltin or any of the other agents tested. The majority of the class I mutants and one of the class II mutants exhibit cold sensitivity of the oligomycin resistance, i.e. they lose resistance at the non‐permissive temperature of 20°C, and this provides a further basis for classification of the mutants. The growth rates of the majority of these resistant mutants from both classes were unaltered from the wild type and the growth yield of the class II mutants was also the same as that of the parental strains. The growth yield of the class I mutants, however, was 15–20% less than that of the wild type. No differences in mitochondrial morphology or of the number of mitochondria per cell were seen on examination by the electron microscope. The isolation and properties of specific mitochondrial oligomycin‐resistant mutants supports the biochemical evidence for different sites of action of oligomycin, triethyltin and uncoupling agents on energy‐conservation reactions.