PT - JOURNAL ARTICLE ED - , TI - Uncoupled to Survive AID - 10.1126/stke.2722005tw70 DP - 2005 Feb 22 TA - Science's STKE PG - tw70--tw70 VI - 2005 IP - 272 4099 - http://stke.sciencemag.org/content/2005/272/tw70.short 4100 - http://stke.sciencemag.org/content/2005/272/tw70.full SO - Sci. STKE2005 Feb 22; 2005 AB - Cellular oxidative damage caused by reactive oxygen species (ROS) is thought to affect life span. Mitochondria synthesize adenosine triphosphate (ATP) through an electron transport chain that establishes a gradient of protons across the mitochondrial membrane. Free radicals are a by-product of this energy-generated process. However, resident uncoupling proteins (UCPs) can disrupt this gradient, decreasing both ATP and ROS production. Fridell et al. demonstrate that the life span of adult fruit flies can be extended through the action of mitochondrial UCPs. Human UCP2 was expressed in the mitochondria of neurons in adult flies. Although this resulted in an increase in mitochondrial respiration, a decrease in hydrogen peroxide production was observed in flies' heads. This correlated with a decrease in oxidative damage and an increase in the life span of flies by up to 28%. Although a decrease in reproductive and physical capabilities has been considered a trade-off for an increased life span, these two activities were normal in flies overexpressing UCP2 in neurons. The authors speculate that altering mitochondrial respiration in the neurons of other adult organisms could have a similar effect on increasing life span. Y.-W. C. Fridell, A. Sanchez-Blanco, B. A. Silvia, S. L. Helfand, Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly. Cell Metabolism 1, 145-152 (2005). [Online Journal]