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NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast |
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| Authors: | María Jiménez-Hidalgo Carlos Santos-Ocaña Sergio Padilla José M Villalba Guillermo López-Lluch Alejandro Martín-Montalvo Robin K Minor David A Sinclair Rafael de Cabo Plácido Navas |
| Institution: | 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; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14014 Córdoba, Spain; Paul F. Glenn Laboratories for the Biological Mechanism of Aging, Department of Pathology, Harvard Medical School, Harvard, MA 02115, USA; Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA |
| Abstract: | 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. |
| Keywords: | chronological lifespan coenzyme Q coenzyme Q reductase dietary restriction NQR1 Plasma membrane replicative lifespan |