Biogenesis of mitochondria: 12. The effects of aminoglycoside antibiotics on the mitochondrial and cytoplasmic protein-synthesizing systems of Saccharomyces cerevisiae

Abstract

The aminoglycoside antibiotics can be divided into two groups on the basis of their effects on Saccharomyces cerevisiae. The first group, consisting of neamine, kanamycin, streptomycin, and viomycin had only minor effects on the growth of yeast cells and on in vitro protein synthesis. The second group, comprising neomycin B, neomycin C, and paromomycin, had complex effects on the growth and survival of yeast cells, and potently inhibited the in vitro incorporation of amino acids into protein by mitochondria and by cytoplasmic ribosomes. The effects of the neomycins and paromomycin on the growth of yeast cells in media containing either fermentable or non-fermentable substrate indicated that in vivo these antibiotics differentiated only marginally between the mitochondrial and cytoplasmic ribosomal protein-synthesising systems. In marked contrast, the incorporation of amino acids by the mitochondrial protein-synthesizing system in vitro was considerably more sensitive to the neomycins and paromomycin than was the cytoplasmic ribosomal system. A probable explanation of this discrepancy is proposed. The mitochondrial protein-synthesizing system of rat liver was compared with that of yeast, and was found to differ in being insensitive to the neomycins and paromomycin. The possible significance of this phylogenetic difference is discussed.