Biogenesis of mitochondria

Protein synthesis in intact rat liver mitochondria is strongly inhibited by chloramphenicol, mikamycin, carbomycin, and spiramycin but is insensitive to erythromycin, lincomycin, and paromomycin. We have investigated methods of damaging the mitochondrial membrane to destroy any possible permeability barriers to these latter antibiotics. Criteria to demonstrate the access of antibiotics to the mitochondria have been based on the finding that paromomycin at 1000 μg/ml inhibits mitochondrial respiration when the mitochondrial membrane has been sufficiently damaged. Under conditions where membrane damage permits free access of paromomycin, neither this antibiotic nor erythromycin nor lincomycin has a specific inhibitory effect on protein synthesis. The possibility is discussed that the evolution of the ribosome from the bacterial ribosome through the yeast mitochondrial ribosome to the mammalian mitochondrial “miniribosome” may be expressed in the loss of certain antibiotic-binding proteins of the protein-synthesizing system.