Regulation of yeast chronological life span by TORC1 via adaptive mitochondrial ROS signaling.

Authors: Pan Y; Schroeder EA; Ocampo A; Barrientos A; Shadel GS

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 tor1Delta 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.

Keywords: *Adaptation, Physiological/drug effects; Colony Count, Microbial; Dinitrophenols/pharmacology; Gene Knockout Techniques; Membrane Potential, Mitochondrial/drug effects/genetics; Microbiological Processes/drug effects/genetics; Mitochondria/drug effects/*metabolism; Multiprotein Complexes/genetics/*metabolism; Oxygen Consumption/genetics; Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*genetics/metabolism; Protein Kinases/genetics/metabolism; Protein-Serine-Threonine Kinases/genetics/metabolism; Saccharomyces cerevisiae/drug effects/growth & development/*physiology; Saccharomyces cerevisiae Proteins/antagonists & inhibitors/*genetics/metabolism; Sirolimus/pharmacology; Superoxides/*metabolism; Vitamin K 3/pharmacology
Journal: Cell metabolism
Volume: 13
Issue: 6
Pages: 668-78
Date: June 7, 2011
PMID: 21641548
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Citation:

Pan Y, Schroeder EA, Ocampo A, Barrientos A, Shadel GS (2011) Regulation of yeast chronological life span by TORC1 via adaptive mitochondrial ROS signaling. Cell metabolism 13: 668-78.


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