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

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Authors

Park, Thomas J.
Reznick, Jane
Peterson, Bethany L.
Blass, Gregory
Omerbasic, Damir
Bennett, Nigel Charles
Henning, P.
Kuich, J.L.
Zasada, Christin
Browe, Brigitte M.

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Volume Title

Publisher

American Association for the Advancement of Science

Abstract

The African naked mole-rats’ (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 (KHK) 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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Keywords

Anoxia, Oxygen deprivation, Fructose-driven glycolysis, Naked mole-rat (Heterocephalus glaber)

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Citation

Park, TJ, Reznick, J, Peterson, BL, Blass, G, Omerbasic, D, Bennett, NC et al, 2017, 'Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat', Science, vol. 356, no. 6335, pp. 307-311.