Involvement of Drosophila Uncoupling Protein 5 in Metabolism and Aging

Abstract

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. M ITOCHONDRIAL uncoupling proteins (UCPs)affect oxidative phosphorylation by reducing the amount of ATP that can be generated from oxidative metabolism (Ricquier 2005). The existence of an evolutionarily conserved mechanism of energy loss through UCP activities in all four eukaryotic kingdoms suggests beneficial functional roles for these proteins in the regulation of energy metabolism (Ricquier and Bouillaud 2000). UCP studies using mammalian systems have been proven to be difficult and have yielded inconclusive results, mostly due to the complex physiological regulation of higher organisms. In this study we used Drosophila melanogaster to examine the effect of altering the activity of one of these proteins, UCP5, on the rate of aging, resistance to starvation, and other parameters that reflect energy production and use. Our data showed that eliminating UCP5 function has a great impact on fly metabolic homeostasis since these flies are highly sensitive to food deprivation, live longer than controls on low-calorie diets, have a decreased level of fertility, and gain less weight than controls on high-calorie diets.The electron transport chain in the mitochondria uses the energy from high-energy electrons released during oxidative metabolism to establish a proton gradient across the inner mitochondrial membrane. In aerobic organisms, the vast majority of ATP is produced in the mitochondria via ATP synthase, which captures

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

“…They had a lower body composition of sugars (glucose and trehalose), and during starvation, their triglyceride reserves were used up faster compared to controls. These data indicate that DmUCP5 is important for maintaining metabolic homeostasis in the fly and might influence the hormonal control of metabolism (Sanchez-Blanco et al 2006).…”

“…Previous studies have indicated the presence of two UCP isoforms in insects, UCP4 and/or UCP5 (Jezek 2002; Sanchez-Blanco et al 2006). Therefore, polyclonal antibodies raised against human UCP4 and rat UCP5 were used in total mitochondrial proteins to evaluate the presence of UCP in fat body and muscle from the cockroach G. coquereliana.…”

“…DmUCP5 is expressed throughout fly development but at a higher level in adults where it is expressed most abundantly in the head. Later studies with DmUCP5 knockout flies indicated the involvement of DmUCP5 in D. melanogaster metabolism and aging (Sanchez-Blanco et al 2006). DmUCP5 knockout flies were highly sensitive to starvation stress and gained less weight compared to controls on high calorie diets.…”

“…The functional characterization of D. melanogaster UCP in the heterologous yeast system (Fridell et al 2004) and the loss-of-function investigations using UCP5 knockout flies (Sanchez-Blanco et al 2006) are the only studies on function and the metabolic importance of UCPs in insects. Thus, the aim of the present study was to identify molecularly and to characterize functionally Gromphadprhina coquereliana UCP (GcUCP).…”

Research on mitochondria and aging, 2006–2007

“…and the effects of CR, sirtuins and resveratrol on mitochondrial function (Haigis et al ., 2006;Lagouge et al ., 2006;Lopez-Lluch et al ., 2006;Nemoto et al ., 2006;Sanchez-Blanco et al ., 2006). Given the intense activity in the field, there should be many more illuminating discoveries just over the horizon.…”