Studies on energy-linked reactions: modified mitochondrial ATPase of oligomycin-resistant mutants of Saccharomyces cerevisiae.

TLDR: The results support the conclusion that oligomycin resistance is due to modification of mitochondrially coded and mitochondRIally synthesised subunits of the oligomyin-sensitive ATPase (ATP synthetase) complex.

Abstract: 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 OLI and OLII 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-sensitivity-conferring 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.