Biogenesis of mitochondria 34

Summary

Mutants of the yeast Saccharomyces cerevisiae have been isolated in this laboratory which show increased resistance to a number of structurally and functionally unrelated antibiotics such as mikamycin, chloramphenicol, oligomycin and tetracycline (Bunn et al., 3971). When a multiply resistant haploid strain was crossed to an antibiotic sensitive strain, the resultant diploid progeny were completely resistant to chloramphenicol and oligomycin. However, the progeny showed different responses to mikamycin depending upon the concentration of antibiotic, all showed resistance to 25 μg/ml but only about half were resistant to high levels of mikamycin (>100 μg/ml). Detailed genetic analyses has shown that resistance to high levels of mikamycin is the result of a phenotypic interaction between two mutations, one nuclear and the other mitochondrial. The nuclear mutation by itself confers resistance to a number of antibiotics including chloramphenicol, oligomycin and mikamycin at a level of 25 μg/ml. The mitochondrial mutation increases cellular resistance to mikamycin from 3 μg/ml to about 8 μg/ml. When the two mutations occur together in a cell, resistance to mikamycin is increased to at least 800 μg/ml, the limit of solubility. Thus, the phenotypie interaction between these two mutations is not additive but synergistic.

When cells containing the cytoplasmic [mik1-r] mutation are treated with ethidium bromide to produce ϱ ^° cells (no mtDNA), the [mik1-r] determinant is lost, indicating that this mutation is located in the mitochondrial DNA. Recombination analyses with other mitochondrial markers indicates a marker order of [oli1-r mik1-r ery1-r] with [mik1-r] showing tighter linkage to the [oli1-r] marker.