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Modular polyketide synthases and nonribosomal peptide synthetases are molecular assembly lines consisting of several multienzyme subunits that undergo dynamic self-assembly to form a functional mega-complex. N-and C-terminal docking domains are usually responsible for Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Oligomycin resistance is expressed at the mitochondrial and submitochondrial levels in oligomycin-resistant mutants of Saccharomyces cerevisiae. Studies of the mitochondrial ATPase and Pi-ATP exchange reaction indicate that a modification of the mitochondrial ATPase (ATP-synthetase) complex is involved. The specific resistance at the mitochondrial level to oligomycin and related inhibitors such as ossamycin, rutamycin and peliomycin and the lack of resistance to other inhibitors of mitochondrial ATP synthetase (triethyltin sulphate, venturicidin, aurovertin, Dio-9) correlate with whole cell studies and provide further evidence for a specific modification of an inhibitor site on the mitochondrial inner membrane.Mitochondrial mutants which map at the OL I and OL I1 loci can be differentiated biochemically by their sensitivity to oligomycin of mitochondrial ATPase and the pH 9.5/pH 6.5 ATPase activity ratios.Studies utilising F1-ATPase from wild type and oligomycin-resistant mutants indicate that oligomycin resistance is due to a modification of a membrane-bound component of the mitochondrial ATP-synthetase complex and not to a modification of F1-ATPase or the oligomycin-sensitivityconferring protein.Partially purified oligomycin-sensitive ATPase preparations (Triton X-100 extracts) retain the sensitivity (resistance) and specificity of the original membrane-bound system in mitochondria. Purified oligomycin-sensitive ATPase preparations also retain the specificity of the original membrane preparation but the sensitivity to inhibitors is partially modified. The results support the conclusion that oligomycin resistance is due to modification of mitochondrially coded and mitochondrially synthesised subunits of the oligomycin-sensitive ATPase (ATP synthetase) complex. There is no correlation of oligomycin resistance with the ergosterol concentration of yeast cells, yeast mitochondria or mitochondrial ATPase.The isolation of yeast mitochondrial mutants resistant to inhibitors and uncouplers of mitochondrial energy conservation systems provides a genetic probe of the inhibitor binding sites of the membranebound ATP-synthetase complex and studies of these mutants may provide information as to the components and the organisation of the mitochondrial energy conservation system [l].Previous studies [2,3] have described the isolation of oligomycin-resistant mutants of Saccharomyces cerevisiae and their phenotypic subdivision into two Abbreviations. mtDNA, mitochondrial DNA; OL I and OL I1 mutants, mitochondrial mutants which map at the OL I (01) and OL I1 (0x1) loci on mtDNA, respectively [4,51.Enzyme. ATPase or ATP phosphohydrolase (EC 3.6.

The genetics of the two major phenotypic classes of oligomycin-resistant yeast mutants have been investigated. All the class I1 mutants (oligomycin specific) tested show typical cytoplasmic inheritance and the determinants appear located on mtDNA. Evidence is presented that this type of resistance can be conferred by a t least two distinct groups of nonallelic cytoplasmic determinants. The class I mutants which show cross resistance to a variety of inhibitors and uncouplers of energy conservation reactions exhibit behaviour on genetic analysis which is not fully understood. Tetrad analysis indicates that a nuclear gene is concerned but many anomalous observations, discussed here, suggestive of the involvement of a cytoplasmic element remain to be explained.The proceeding paper in this series [l] has dealt with the phenotypic subdivision of oligomycinresistant mutants into two main classes, class I and class 11, and with the physiology and morphology of both classes of mutants. This paper deals with the genetic characterisation of these same mutants. The known locus of action of oligomycin on the mitochondrial ATP-synthetase complex [2,3] suggested the possibility that some of the mutants might be cytoplasmically inherited especially as the ATPase activity of Q-strains has been shown to be oligomycin insensitive [4]. The genetic analysis of the mutants therefore stresses the investigation of the cytoplasmic or nuclear mode of inheritance of oligomycin resistance in representative mutants drawn from both classes I and 11. Strains in which the oligomycinresistant determinant exhibited cytoplasmic inheritance were examined for correlation of the resistance determinant with mtDNA.