Inhibition of mitochondrial-protein synthesis in rat small-intestinal epithelium.

Abstract

Because of its very fast turnover, implying a rapid biogenesis of intestinal mitochondria, rat‐small‐intestinal epithelium was regarded as an excellent target for the action of chloramphenicol and oxytetracycline, specific inhibitors of mitochondrial protein synthesis. With constant blood levels of chloramphenicol and oxytetracycline above 10 μg/ml the levels of the mitochondrial cytochromes aa3, b and c1 in villous and crypt cells decreased gradually until a minimum level was reached after about 48 h of treatment. The rapid onset of the fall in cytochrome aa3 content within the villous cells indicated a further synthesis of this enzyme outside the proliferative compartment of the crypt. No significant change was observed in the cellular contents of numerous other mitochondrial and extramitochondrial enzymes, confirming the restricted function of the mitochondrial protein‐synthesizing machinery for the biosynthesis of mammalian mitochondria. Prolonged treatment with oxytetracycline, but not with chloramphenicol, caused a severe damage of the villous epithelium. This toxic effect was probably not related to the lowered cytochrome content of the mitochondria.