Title

Involvement of Drosophila uncoupling protein 5 in metabolism and aging

Date of Completion

January 2005

Keywords

Biology, Molecular|Biology, Genetics|Biology, Animal Physiology

Degree

Ph.D.

Abstract

A novel uncoupling protein, UCP5, has recently been characterized as a functional mitochondrial uncoupler in Drosophila. Here we demonstrate that UCP5 knock-out (UCP5KO) flies are highly sensitive to starvation stress, a phenotype that can be reversed by ectopic neuronal expression of UCP5. UCP5KO flies live longer than controls on low calorie diets, have a decreased level of fertility, and gain less weight than controls on high calorie diets. However, isolated mitochondria from UCP5KO flies display the same respiration patterns as controls. Furthermore, total ATP levels in both UCP5KO and control flies are comparable. UCP5KO flies have lower body composition of sugars, and during starvation stress their triglyceride reserves are depleted more rapidly than controls. We also show that overexpressing ucp5 in the neurosecretory cells that secrete adipokinetic hormone, the insect equivalent of glucagon, leads to starvation sensitive flies. In summary, these data indicate that UCP5 is important to the maintenance of metabolic homeostasis in the fly. Based on these data we hypothesize that UCP5 influences the hormonal control of metabolism. ^