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National Institute of Environmental Health Sciences

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Publication Detail

Title: Neuronal expression of a single-subunit yeast NADH-ubiquinone oxidoreductase (Ndi1) extends Drosophila lifespan.

Authors: Bahadorani, Sepehr; Cho, Jaehyoung; Lo, Thomas; Contreras, Heidy; Lawal, Hakeem O; Krantz, David E; Bradley, Timothy J; Walker, David W

Published In Aging Cell, (2010 Apr)

Abstract: The 'rate of living' theory predicts that longevity should be inversely correlated with the rate of mitochondrial respiration. However, recent studies in a number of model organisms, including mice, have reported that interventions that retard the aging process are, in fact, associated with an increase in mitochondrial activity. To better understand the relationship between energy metabolism and longevity, we supplemented the endogenous respiratory chain machinery of the fruit fly Drosophila melanogaster with the alternative single-subunit NADH-ubiquinone oxidoreductase (Ndi1) of the baker's yeast Saccharomyces cerevisiae. Here, we report that expression of Ndi1 in fly mitochondria leads to an increase in NADH-ubiquinone oxidoreductase activity, oxygen consumption, and ATP levels. In addition, exogenous Ndi1 expression results in increased CO2 production in living flies. Using an inducible gene-expression system, we expressed Ndi1 in different cells and tissues and examined the impact on longevity. In doing so, we discovered that targeted expression of Ndi1 in fly neurons significantly increases lifespan without compromising fertility or physical activity. These findings are consistent with the idea that enhanced respiratory chain activity in neuronal tissue can prolong fly lifespan.

PubMed ID: 20089120 Exiting the NIEHS site

MeSH Terms: Animals; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism*; Cell Respiration; Cell Survival; Drosophila melanogaster/enzymology; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology*; Female; Fertility; Longevity; Male; Mitochondria/metabolism; Neurons/cytology; Neurons/drug effects; Neurons/metabolism*; Organ Specificity; Oxidative Stress; Rotenone/toxicity; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism*; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism*

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