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

Thomas J. Park(University of Illinois Chicago), Jane Reznick(Max Delbrück Center), Bethany L. Peterson(University of Illinois Chicago), Gregory Blass(University of Illinois Chicago), Damir Omerbašić(Max Delbrück Center), Nigel C. Bennett(University of Pretoria), P. Henning J. L. Kuich(Max Delbrück Center), Christin Zasada(Max Delbrück Center), Brigitte M. Browe(University of Illinois Chicago), Wiebke Hamann(Max Delbrück Center), Daniel T. Applegate(University of Illinois Chicago), Michaël Radkë(Max Delbrück Center), Tetiana Kosten(Max Delbrück Center), Heike Lutermann(University of Pretoria), Victoria Gavaghan(University of Illinois Chicago), Ole Eigenbrod(Max Delbrück Center), Valérie Bégay(Max Delbrück Center), Vince G. Amoroso(University of Illinois Chicago), Vidya Govind(University of Illinois Chicago), Richard D. Minshall(University of Illinois Chicago), Ewan St. John Smith(University of Cambridge), John Larson(University of Illinois Chicago), Michael Gotthardt(Max Delbrück Center), Stefan Kempa(Max Delbrück Center), Gary R. Lewin(Max Delbrück Center)
Science
April 20, 2017
10.1126/science.aab3896
Cited by 648Open Access
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Abstract

) 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.

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