Gambini, J., Gomez-Cabrera, M.C., Borras, C., Valles, S.L., Lopez-Grueso, R., Martinez-Bello, V.E., Herranz, D., Pallardo, F.V., Tresguerres, J.A., Serrano, M., Viña, J. (2011). Free [NADH]/[NAD(+)] regulates sirtuin expression.  Arch. Biochem. Biophys. 512(1): 24--29.

FBrf0214039

Research paper

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.