Mitochondrial chloramphenicol-resistant mutants can have deficiencies in energy metabolism.

Three pairs of mouse CAP-R PYR-IND OLI-R mitochondrial mutants, and the corresponding CAP-S parental lines, were assayed to determine if cellular expression of these phenotypes was accompanied by changes in cellular energy metabolism: glycolysis, cellular respiration, citric acid cycle activity, and mitochondrial electron transport. Relative to its parental CAP-S line, the SVT2 CAP-R mutant had no significant deficiencies in any of the pathways analyzed. In contrast, the LA9 and SVA31 CAP-R mutants showed significant reductions in cellular respiration. At the biochemical level, respiration deficiency was accompanied by derangements in mitochondrial electron transport. It was also found that the CAP-R mutants had very high levels of glycolysis when the cells were maintained in the presence of chloramphenicol. The possibility is discussed that the sequence changes in the mitochondrial large rRNA gene which determine chloramphenicol resistance can also result, at least in some cases, in reduced levels of mitochondrial biogenesis, leading to respiration deficiency. The PYR-IND and OLI-R phenotypes, which also appear to be encoded by the CAP-R mutations, may result from a compensatory increase in glycolysis-generated ATP or metabolic intermediates.