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

  1. María Jiménez-Hidalgo1,
  2. Carlos Santos-Ocaña1,
  3. Sergio Padilla1,
  4. José M. Villalba2,
  5. Guillermo López-Lluch1,
  6. Alejandro Martín-Montalvo1,
  7. Robin K. Minor4,
  8. David A. Sinclair3,
  9. Rafael De Cabo4,
  10. Plácido Navas1

Article first published online: 23 FEB 2009

DOI: 10.1111/j.1474-9726.2009.00461.x

Issue

Aging Cell

Aging Cell

Volume 8, Issue 2, pages 140–151, April 2009

Additional Information

How to Cite

Jiménez-Hidalgo, M., Santos-Ocaña, C., Padilla, S., Villalba, J. M., López-Lluch, G., Martín-Montalvo, A., Minor, R. K., Sinclair, D. A., De Cabo, R. and Navas, P. (2009), NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast. Aging Cell, 8: 140–151. doi: 10.1111/j.1474-9726.2009.00461.x

Author Information

  1. 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

  2. 2

    Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14014 Córdoba, Spain

  3. 3

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

  4. 4

    Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA

* 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

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

Publication History

  1. Issue published online: 26 MAR 2009
  2. Article first published online: 23 FEB 2009
  3. Accepted for publication 5 January 2009

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Keywords:

  • chronological lifespan;
  • coenzyme Q;
  • coenzyme Q reductase;
  • dietary restriction;
  • NQR1;
  • Plasma membrane;
  • replicative lifespan

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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