• Open Access

NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast

Authors

  • María Jiménez-Hidalgo,

    1. 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
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  • Carlos Santos-Ocaña,

    1. 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
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  • Sergio Padilla,

    1. 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
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  • José M. Villalba,

    1. Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14014 Córdoba, Spain
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  • Guillermo López-Lluch,

    1. 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
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  • Alejandro Martín-Montalvo,

    1. 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
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  • Robin K. Minor,

    1. Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA
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  • David A. Sinclair,

    1. Paul F. Glenn Laboratories for the Biological Mechanism of Aging, Department of Pathology, Harvard Medical School, Harvard, MA 02115, USA
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  • Rafael De Cabo,

    1. Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA
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  • Plácido Navas

    1. 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
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  • These authors, María Jiménez-Hidalgo and Carlos Santos-Ocaña, have contributed equally to this work.


Plácido Navas, 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. Tel.: +34 954349385; fax: +34 954349376; e-mail: pnavas@upo.es
Rafael de Cabo, Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Tel.: +1 4105588510; fax: +1 4105588302; e-mail: decabora@grc.nia.nih.gov

Summary

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.

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