Nuclear Inheritance of Oligomycin Resistance in Mouse L Cells

The inheritance of oligomycin resistance was studied in three mouse L-cell mutants, OLI 2, OLI 4, and OLI 14. All three mutants had previously been shown to have oligomycin-resistant mitochondrial ATPase activity. In addition, OLI 14 has DCCD-resistant mitochondrial ATPase activity and an altered DCCD-binding protein. Oligomycin-resistant cells were enucleated and fused with oligomycin-sensitive cells under a variety of selective regimes designed to allow growth of oligomycin-resistant cybrids. No transfer of oligomycin resistance via the cytoplasm of OLI 2, OLI 4, or OLI 14 was detected. In contrast, oligomycin resistance was transferred with the karyoplasts of OLI 14 in karyoplast-cell fusions. Fusions between OLI 14 cells and oligomycin-sensitive cells also produced oligomycin-resistant hybrids. Transfer of oligomycin resistance in the karyoplast-cell and cell-cell fusions were demonstrated at the level of the mitochondrial ATPase. These results indicate that oligomycin resistance in OLI 14 is most likely under nuclear control. Furthermore, nuclear inheritance of oligomycin resistance in a mutant with a modified DCCD-binding protein suggests that the gene for the DCCD-binding protein is encoded in the nucleus of mammalian cells.