Neuronal expression of a single-subunit yeast  NADH-ubiquinone oxidoreductase (Ndi1) extends  Drosophila lifespan.
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.
Bahadorani
Sepehr
S
Department of Physiological Science, University of California, Los Angeles, Los Angeles, CA 90095-1527, USA.
Cho
Jaehyoung
J
Lo
Thomas
T
Contreras
Heidy
H
Lawal
Hakeem O
HO
Krantz
David E
DE
Bradley
Timothy J
TJ
Walker
David W
DW
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019069:Cell Respiration; D002470:Cell Survival; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility; D008136:Longevity; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D018384:Oxidative Stress; D012402:Rotenone / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C433703:Ndj1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012402:Rotenone