Format

Send to

Choose Destination
Science. 2017 Apr 21;356(6335):307-311. doi: 10.1126/science.aab3896.

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

Author information

1
Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. glewin@mdc-berlin.de tpark@uic.edu.
2
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
3
Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
4
Department of Zoology and Entomology, University of Pretoria, Pretoria, Republic of South Africa.
5
Integrative Proteomics and Metabolomics, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
6
Neuromuscular and Cardiovascular Cell Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
7
German Centre for Cardiovascular Research (DZHK), Berlin, Germany.
8
Departments of Anesthesiology and Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
9
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
10
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
11
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany. glewin@mdc-berlin.de tpark@uic.edu.
12
Excellence Cluster Neurocure, Charité Universitätsmedizin Berlin, Berlin, Germany.

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.

PMID:
28428423
DOI:
10.1126/science.aab3896
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center