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

TY - JOUR

T1 - Free [NADH]/[NAD+] regulates sirtuin expression

AU - Gambini, Juan

AU - Gomez-Cabrera, Mari Carmen

AU - Borras, Consuelo

AU - Valles, Soraya L.

AU - Lopez-Grueso, Raul

AU - Martinez-Bello, Vladimir E.

AU - Herranz, Daniel

AU - Pallardo, Federico V.

AU - Tresguerres, Jesus A.F.

AU - Serrano, Manuel

AU - Viña, Jose

N1 - Funding Information: This work was supported by Grants SAF2008-00270; SAF2009-08334; SAF2010-19498; from the Spanish Ministry of Education and Science (MEC); PROMETEO/2010/074 from the Consellería de Educación de la Generalitat Valenciana. ISCIII2006-RED13-027 from the “Red Temática de investigación cooperativa en envejecimiento y fragilidad (RETICEF)”, EU Funded COSTB35 and DPS2008-06968 from Spanish Ministry of Innovation and Science. This study has been co-financed by FEDER funds from the European Union.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

KW - Drosophila

KW - Ethanol

KW - Exercise

KW - Lactate

KW - Pyruvate

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=79959820041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959820041&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.abb.2011.04.020

DO - https://doi.org/10.1016/j.abb.2011.04.020

M3 - Article

C2 - 21575591

SN - 0003-9861

VL - 512

SP - 24

EP - 29

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

IS - 1

ER -