Abstract
Here we show that yeast strains with reduced target of rapamycin (TOR) signaling have greater overall mitochondrial electron transport chain activity during growth that is efficiently coupled to ATP production. This metabolic alteration increases mitochondrial membrane potential and reactive oxygen species (ROS) production, which we propose supplies an adaptive signal during growth that extends chronological life span (CLS). In strong support of this concept, uncoupling respiration during growth or increasing expression of mitochondrial manganese superoxide dismutase significantly curtails CLS extension in tor1Δ strains, and treatment of wild-type strains with either rapamycin (to inhibit TORC1) or menadione (to generate mitochondrial ROS) during growth is sufficient to extend CLS. Finally, extension of CLS by reduced TORC1/Sch9p-mitochondrial signaling occurs independently of Rim15p and is not a function of changes in media acidification/composition. Considering the conservation of TOR-pathway effects on life span, mitochondrial ROS signaling may be an important mechanism of longevity regulation in higher organisms.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological* / drug effects
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Colony Count, Microbial
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Dinitrophenols / pharmacology
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Gene Knockout Techniques
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / genetics
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Microbiological Phenomena / drug effects
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Microbiological Phenomena / genetics
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Oxygen Consumption / genetics
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Phosphatidylinositol 3-Kinases / genetics*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / physiology*
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Sirolimus / pharmacology
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Superoxides / metabolism*
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Vitamin K 3 / pharmacology
Substances
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Dinitrophenols
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Multiprotein Complexes
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Phosphoinositide-3 Kinase Inhibitors
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Saccharomyces cerevisiae Proteins
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Superoxides
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Vitamin K 3
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Protein Kinases
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Rim15 protein, S cerevisiae
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TOR1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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SCH9 protein, S cerevisiae
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Sirolimus