Citric acid cycle: a mainstream metabolic pathway influencing life span in Drosophila melanogaster?

The role of the citric acid cycle enzyme NADP-dependent isocitrate dehydrogenase (IDH-NADP) and its allele product variants in resisting the oxidative agent paraquat, was analyzed among descendants of reciprocal crosses between fast developmental time short-lived individuals (F-) and slow developmental time long-lived ones (S+), in Drosophila melanogaster. Taking preadult developmental time into account, the data suggested that IDH-NADP differences in enzymatic activity between electrophoretically fast and slow allele product variants could play an important role in paraquat resistance and longevity, because individuals with slow developmental time bearing the fast electrophoretic variant of IDH-NADP ("fast" allele) were the most resistant. The fast electrophoretic variant of this enzyme is known to be the most active one and its activity is related to increased reduction of NADP to NADPH. This process could be very important for an effective balance between several pathways that use NADPH as precursor molecules and the oxidative stress defense system that uses it as an oxygen free radical reductor. We also reported a strong maternal effect on these traits, because survivors of a paraquat bioassay carrying cytoplasm inherited from slow developmental long-lived females (S+ cytoplasm) showed the highest frequency of the fast electrophoretical variant of IDH-NADP.