Free [NADH]/[NAD+] regulates sirtuin expression

Juan Gambini, Mari Carmen Gomez-Cabrera, Consuelo Borras, Soraya L. Valles, Raul Lopez-Grueso, Vladimir E. Martinez-Bello, Daniel Herranz, Federico V. Pallardo, Jesus A.F. Tresguerres, Manuel Serrano, Jose Viña

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD+] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD+] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[NAD+] ratio, which is a major sensor for metabolite availability conserved from invertebrates to vertebrates.

Original languageAmerican English
Pages (from-to)24-29
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number1
StatePublished - Aug 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


  • Drosophila
  • Ethanol
  • Exercise
  • Lactate
  • Pyruvate
  • Rat


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