Inhibition of mitochondrial synthesis in yeast by erythromycin: cytoplasmic and nuclear factors controlling resistance

Abstract

Erythromycin-resistant mutants were separated into two categories showing Mendelian and non-Mendelian inheritance of resistance respectively. The cytoplasmic factor was located in the mitochondrion based on the fact that the loss of the mitochondrial genetic unit associated with the petite mutation (the ρ factor, assumed to be the mitochondrial DNA) resulted in a corresponding permanent loss of resistance. Conversely, the petite mutation in gene resistant mutants had no effect on the inheritance of resistance.Analysis of vegetative and sexual progeny of isolated zygotes from a number of crosses between resistant and sensitive strains indicated that different mitochondrial types, both sensitive and resistant, co-exist in the yeast cell and are distributed at random among daughter cells under non-selective conditions. Only resistant mitochondria are in evidence if zygotes are put down to proliferate on medium containing the antibiotic.Resistant strains were tested for retention of resistance following anaerobic culture (known to cause disruption of mitochondria). The cytoplasmic mutants retained their resistance but two gene-resistant mutants tested both lost their resistance. It was suggested in the latter case that resistance is dependent on the existence of intact mitochondrial membrane (possibly inner membrane). In the former mutants the mechanism of resistance may be the alteration of one or other of the components of the protein-synthesizing system of the organelle.