| Literature DB >> 28428423 |
Thomas J Park1, Jane Reznick2, Bethany L Peterson3, Gregory Blass3, Damir Omerbašić2, Nigel C Bennett4, P Henning J L Kuich5, Christin Zasada5, Brigitte M Browe3, Wiebke Hamann6, Daniel T Applegate3, Michael H Radke6,7, Tetiana Kosten2, Heike Lutermann4, Victoria Gavaghan3, Ole Eigenbrod2, Valérie Bégay2, Vince G Amoroso3, Vidya Govind3, Richard D Minshall8, Ewan St J Smith9, John Larson10, Michael Gotthardt6,7, Stefan Kempa5, Gary R Lewin11,12.
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.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28428423 DOI： 10.1126/science.aab3896
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728