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Originally published as Genetics Published Articles Ahead of Print on December 30, 2005.
Genetics, Vol. 172, 1699-1710, March 2006, Copyright © 2006
doi:10.1534/genetics.105.053389
Involvement of Drosophila Uncoupling Protein 5 in Metabolism and Aging
Adolfo Sánchez-Blanco1, Yih-Woei C. Fridell and Stephen L. Helfand2
Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030
2 Corresponding author: Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Laboratories for Molecular Medicine, 70 Ship St., Room 407, Providence, RI 02903.
E-mail: stephen_helfand{at}brown.edu
A novel uncoupling protein, UCP5, has recently been characterized as a functional mitochondrial uncoupler in Drosophila. Here we demonstrate that UCP5 knockout (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 a lower body composition of sugars, and during starvation stress their triglyceride reserves are depleted more rapidly than controls. Taken together, these data indicate that UCP5 is important to maintain metabolic homeostasis in the fly. We hypothesize that UCP5 influences hormonal control of metabolism.
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