Biochemical and ultrastructural studies on flight muscle mitochondria from the blowfly Calliphora erythrocephala following treatment by chloramphenicol and ethidium bromide.

Adult blowflies were injected during the first day after eclosion with various concentrations of the drugs chloramphenicol and ethidium bromide. Previous experiments had shown that these drugs inhibit mitochondrial protein synthesis and at high doses increase mortality. Mitochondria isolated from blowflies 24 h after drug injection revealed a considerable decrease in oxidation rates when pyruvate plus proline were used as substrates. There was also a reduction up to 50% in the respiratory control ratios obtained, though there was little change in the measurable ADP: O ratios. This loss in activity was commensurate with the finding that both drugs block the rapid increase in protein synthesis (expressed as mitochondrial protein content) during the period of observation. Examination of the cytochrome difference spectra 24 h after treatment again showed a decline in all major cytochrome peaks with increasing concentration of both drugs. Examination of mitochondrial morphology in situ using electron microscopy revealed degenerative changes 24 h after treatment with high doses of both drugs. In particular, irregular alignment of cristae and extensive vacuolation were observed within the mitochondria. The extent of decreased biochemical activity and morphological damage to mitochondria was clearly dependent on the concentration of drugs administered and such changes may be attributed primarily to a loss of certain polypeptide subunits coded for by mitochondrial DNA and synthesized on mitochondrial ribosomes.