Genetic and hormonal control of cytosolic malate dehydrogenase activity in Drosophila melanogaster.

The activity of Drosophila cytosolic malate dehydrogenase (MDH; EC 1.1.1.40), a key enzyme in the biosynthesis of lipids, was found to be regulated by both the sesquiterpenoid juvenile hormone (JH), and the steroid hormone ecdysone. The responsiveness of MDH to JH largely depended on the developmental stage or endogenous titre of ecdysone. During the early through middle period of the last larval instar, when ecdysone levels are low, MDH responded to JH rapidly by increasing activity, while little or no response was measured in mature larvae (postfeeding stage) and fresh pupae when the endogenous pulse of ecdysone is high. Activity of MDH in ecd1 and su(f)ts67g, two ecdysone-deficient mutants of Drosophila, was increased when compared to wild type controls, and was also sensitive to administration of JH. The differences in MDH activity between ecd1 and su(f)ts67g were negligible indicating a substantial role of ecdysone in the enzyme regulation and minimal or no effect of their genetic backgrounds. Accordingly, another Drosophila mutant, ap4 which is naturally deficient in JH production, displayed significantly reduced activity of MDH in heterozygotic combination, and almost undetectable MDH activity in null homozygote adults. The ap4 phenotype was more strongly manifested in the adult stage than in larvae which showed 7-times lower requirements for JH titre. In addition, high/low sucrose diet fed to wild types or mutants affected the activity of larval MDH, but the enzyme remained sensitive to administration of JH. These results corroborate those described for mammals and provide the first evidence that Drosophila MDH might be under differential hormonal and nutritional control. These data will serve as a basis for further molecular characterization of the Drosophila MDH gene and its regulation.