NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast.
The activity and expression of plasma membrane NADH coenzyme Q reductase is increased by calorie restriction (CR) in rodents. Although this effect is well-established and is necessary for CR's ability to delay aging, the mechanism is unknown. Here we show that the Saccharomyces cerevisiae homolog, NADH-Coenzyme Q reductase 1 (NQR1), resides at the plasma membrane and when overexpressed extends both replicative and chronological lifespan. We show that NQR1 extends replicative lifespan in a SIR2-dependent manner by shifting cells towards respiratory metabolism. Chronological lifespan extension, in contrast, occurs via an SIR2-independent decrease in ethanol production. We conclude that NQR1 is a key mediator of lifespan extension by CR through its effects on yeast metabolism and discuss how these findings could suggest a function for this protein in lifespan extension in mammals.
Jiménez-Hidalgo
María
M
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC and Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, E-41013 Sevilla, Spain.
Santos-Ocaña
Carlos
C
Padilla
Sergio
S
Villalba
José M
JM
López-Lluch
Guillermo
G
Martín-Montalvo
Alejandro
A
Minor
Robin K
RK
Sinclair
David A
DA
de Cabo
Rafael
R
Navas
Plácido
P
D002462:Cell Membrane / Q000378:metabolism*; D019069:Cell Respiration / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D042967:Electron Transport Complex I / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D000431:Ethanol / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D000431:Ethanol; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D042967:Electron Transport Complex I