Studies on the mechanism of the oxygen-induced synthesis of cytochrome oxidase in yeast. Specific effects of benzimidazole on cytochrome-oxidase anabolism.

Abstract

At concentrations where benzimidazole inhibited partially total protein synthesis in yeast, the drug also inhibited protein synthesis mediated by cytoplasmic ribosomes and by isolated mitochondria in vitro. Except for cytochrome oxidase, the effects of benzimidazole on the anabolism of hemoproteins were also partial and unspecific; the induction by oxygen of the particulate cytochromes b and c1, the synthesis of which is determined by the obligate co‐operation of both protein‐synthesizing systems, was not affected more than the induction of catalase, an extramitochondrial hemo‐protein, which is synthesized exclusively in cytoplasm. The drastic inhibition of cytochrome oxidase was the consequence of a specific blocking of cytochrome (a, a3) production. The delayed adaptation to oxygen, following the exclusion of benzimidazole, was characterized by its exceptionally high rate and correlated with the simultaneous increase of hemo‐protein (a, a3) content and the development of cytochrome oxidase activity; the latter activity ruled respiration rate. The process was largely unsensitive to the concerted actions of cycloheximide and chloramphenicol; under identical conditions, the synthesis of other hemoproteins was immediately stopped. The reconstitution of cytochrome oxidase in vivo at the expense of the double set of cytoplasmic and mitochondrial adaptation products, which were simultaneously accumulated, was established by reference to the specific effects of cycloheximide and chloramphenicol. As the prevailing effect of benzimidazole was operationally to switch off the assembly of cytochrome (a, a3), it is inferred that the drug will afford new experimental approaches in further studies of cytochrome oxidase anabolism.