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Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat

Item Type:Article
Title:Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat
Creators Name:Park, T.J. and Reznick, J. and Peterson, B.L. and Blass, G. and Omerbašić, D. and Bennett, N.C. and Kuich, P.H.J.L. and Zasada, C. and Browe, B.M. and Hamann, W. and Applegate, D.T. and Radke, M.H. and Kosten, T. and Lutermann, H. and Gavaghan, V. and Eigenbrod, O. and Bégay, V. and Amoroso, V. G. and Govind, V. and Minshall, R.D. and Smith, E.S.J. and Larson, J. and Gotthardt, M. and Kempa, S. and Lewin, G.R.
Abstract:The African naked mole-rat's (Heterocephalus glaber) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease.
Keywords:Adaptation, Physiological, Anaerobiosis, Brain, Fructokinases, Fructose, Glucose Transporter Type 5, Glycolysis, Lactic Acid, Myocardium, Oxygen, Sucrose, Animals, Mice, Mole Rats
Publisher:American Association for the Advancement of Science
Page Range:307-311
Date:21 April 2017
Additional Information:Copyright © 2017, American Association for the Advancement of Science.
Official Publication:https://doi.org/10.1126/science.aab3896
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