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Genetics of the mammalian oxidative phosphorylation system: Characterization of a new oligomycin-resistant Chinese hamster ovary cell line

Journal Article · · Mol. Cell. Biol.; (United States)
DOI:https://doi.org/10.1128/MCB.2.7.772· OSTI ID:5965215
The properties of a new type of oligomycin-resistant Chinese hamster ovary (CHO) cell line (Oli/sup r/ 2.2) are described in this paper. Oli/sup r/ 2.2 cells were approximately 50,000-fold more resistant to oligomycin than were wild-type CHO cells when tested in glucose-containing medium, but only 10- to 100-fold more resistant when tested in galactose-containing medium. Oli/sup r/ 2.2 cells grew with a doubling time similar to that of wild-type cells both in the presence or absence of oligomycin. Oligomycin resistance in Oli/sup r/ 2.2 cells was stable in the absence of drug. In vitro assays indicated that there was approximately a 25-fold increase in the resistance of the mitochondrial ATPase to inhibition by oligomycin in Oli/sup r/ 2.2 cells, with little change in the total ATPase activity. The electron transport chain was shown to be functional in Oli/sup r/ 2.2 cells. Oli/sup r/ 2.2 cells were cross-resistant to other inhibitors of the mitochondrial ATPase (such as rutamycin, ossamycin, peliomycin, venturicidin, leucinostatin, and efrapeptin) and to other inhibitors of mitochondrial functions (such as chloramphenicol, rotenone, and antimycin). Oligomycin resistance was expressed codominantly in hybrids between Oli/sup r/ 2.2 cells and wild-type cells. Cross-resistance to ossamycin, peliomycin, chloramphenicol, antimycin, venturicidin, leucinostatin, and efrapeptin was also expressed codominantly in hybrids. Fusions of enucleated Oli/sup r/ 2.2 cells with wild-type cells and characterization of the resulting cybrid clones indicated that resistance to oligomycin and ossamycin results from a mutation in both a nuclear gene and a cytoplasmic gene. Cross-resistance to efrapeptin, leucinostatin, venturicidin, and antimycin results from a mutation in only a nuclear gene.
Research Organization:
Biology Programs, The Univ. of Texas at Dallas, Richardson, TX 75080
OSTI ID:
5965215
Journal Information:
Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 2:7; ISSN MCEBD
Country of Publication:
United States
Language:
English