Resveratrol increases glycolytic flux in Saccharomyces cerevisiae via a SNF1-dependet mechanism
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Evidence suggests that AMP protein kinase (AMPK) is the main target of the phytochemical resveratrol (RSV) in mammalian cells. Data also indicates that RSV stimulates glucose metabolism; however, the molecular link between RSV and glucose uptake remains unknown. Herein, we provide evidence indicating that RSV stimulates glycolysis via sucrose non-fermenting 1 gene (SNF1, Saccharomyces cerevisiae orthologous of AMPK). S. cerevisiae cultures treated with 30 μM RSV showed an increase in extracellular acidification rate compared to untreated cells, indicating an elevated glycolytic flux. Also, RSV treatment increased transcription levels of two key glycolytic genes, hexokinase 2 (HXK2) and phosphofructokinase 1 (PFK1), as well as production of NADH. Moreover, RSV treatment inhibited mitochondrial respiration when glucose was used as a carbon source. Importantly, the effects of RSV on glycolysis were dependent of SNF1. Taken together, these findings suggest that SNF1 (AMPK in mammalian systems) is the molecular target of RSV in S. cerevisiae.
KeywordsResveratrol Glucose metabolism Crabtree effect Respiration
This work was financially supported by grants from Instituto Tecnológico Superior de Ciudad Hidalgo (3308.100310) and Universidad Autónoma de Querétaro (FCQ201417). The PROMEP program contributes with a scholarship grant for LAMP. The authors thank to Ana Karen Padilla-Pérez, Cecilia Martínez-Ortiz, Mayra Alejandra Soto-Villagómez, Josué Misael Zamudio-Bolaños, Andrés Carrillo-Garmendia and Maria Irene Cornelio-Martinez for the technical support in kinetic assays.
Conflict of Interest
The authors have no conflicts of interest to declare.
- Gallis JL, Serhan N, Gin H, Couzigou P, Beauvieux MC (2012) Resveratrol plus ethanol counteract the ethanol-induced impairment of energy metabolism: (3)(1)P NMR study of ATP and sn-glycerol-3-phosphate on isolated and perfused rat liver. Pharmacol Res: Off J Ital Pharmacol Soc 65:387–395. doi: 10.1016/j.phrs.2011.12.003 CrossRefGoogle Scholar
- Gancedo JM (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62:334–361Google Scholar
- McCord JM, Fridovich I (1969) Superoxide dismutase an enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055Google Scholar
- Moreira AC, Silva AM, Santos MS, Sardao VA (2013) Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: investigation of the role of gender. Food Chem Toxicol: Int J Publ Br Ind Biol Res Assoc 53:18–26. doi: 10.1016/j.fct.2012.11.031 CrossRefGoogle Scholar
- Sassi N, Mattarei A, Azzolini M, Szabo I, Paradisi C, Zoratti M, Biasutto L (2014) Cytotoxicity of mitochondria-targeted resveratrol derivatives: interactions with respiratory chain complexes and ATP synthase. Biochim Biophys Acta 1837:1781–1789. doi: 10.1016/j.bbabio.2014.06.010 CrossRefGoogle Scholar
- Timmers S, Auwerx J, Schrauwen P (2012) The journey of resveratrol from yeast to human. Aging (Albany NY) 4:146–158Google Scholar
- Vetterli L, Brun T, Giovannoni L, Bosco D, Maechler P (2011) Resveratrol potentiates glucosestimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. J Biol Chem 286:6049–6060. doi: 10.1074/jbc.M110.176842