Expression of yeast NADH dehydrogenase and ascidian alternative oxidase affects metabolism and free radical processes in Drosophila

Objective: The study aimed to investigate the effect of overexpression of alternative mitochondrial enzymes such as yeast NADH dehydrogenase I (NDI1) and alternative oxidase (AOX) on the metabolism, oxidative stress and feeding behavior of the fruit fly Drosophila melanogaster . Experimental flies with expression of NDI1 or AOX were generated using genetic crosses based on the GAL4-UAS system. Results: Flies with NDI1 expression showed increased food consumption, markers of oxidative stress (elevated carbonyl protein content), and increased activity of the detoxification enzyme glutathione- S -transferase, along with decreased activity of key metabolic enzymes including isocitrate dehydrogenase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase. In contrast, AOX -expressing flies had reduced lactate dehydrogenase (LDH) activity, decreased level of lipid peroxides, increased glutathione reductase activity. Lower free glucose levels with elevated glycogen stores was found in AOX -expressing flies. The results indicate that the alternative electron transport chain radically transforms energy and redox metabolism. In particular, NDI1 expression could lead to increased energy demand and compensatory hyperphagia. In contrast, AOX bypasses the main steps of proton gradient generation, reducing superoxide generation.