Modulation between aerobic and anaerobic metabolism in the mutant cell line CdtR-Q

It has recently been shown that the cell line Don Q obtained by mutagenesis of wild type Chinese hamster lung fibroblasts (Don wt), presents a point mutation in the gene coding for UDP-glucose pyrophosphorylase. The persistent low level of UDP-glucose makes Don Q clone resistant to Clostridium difficile toxin B. Starting from the observation that Don Q cells exhibit many large hydrophobic cytoplasmic inclusions, that we have found to be made of neutral lipids, the aerobic metabolism of the two cell lines has been examined. The specific activity of cytochrome oxidase in Don Q cells is more than 5 times lower than that found in Don wt. Also, the activity of Complexes II + III, expressed by the activity of succinate-cytochrome c oxido-reductase, has been found to be lower in Don Q compared to wt cells. On the other hand, NADH-cytochrome c oxido-reductase activity, insensitive to rotenone, is more than doubled in Don Q. In these cells the activity of lactate dehydrogenase is very high, being able to oxidise more than 3,000 nmoles of NADH/min/mg of protein. The results obtained indicate that Don Q cells, in addition to a decreased ability to synthesise UDP-glucose, have an impairment in the respiratory chain. Such an impairment could be correlated to the increased capacity to generate a higher amount of reducing equivalents through the glycolytic activity, which can then be utilised for the synthesis of fatty acids stored in lipid droplets.