A sweet story of metabolic innovation in the naked mole-rat

The naked mole-rat's (Heterocephalus glaber) social and subterranean lifestyle imposes several evolutionary pressures which have shaped its physiology. One example is low oxygen availability in a crowded burrow system which the naked mole-rat has adapted to via several mechanisms. Here we describe a metabolic rewiring which enables the naked mole-rat to switch substrates in glycolysis from glucose to fructose thereby circumventing feedback inhibition at phosphofructokinase (PFK1) to allow unrestrained glycolytic flux and ATP supply under hypoxia. Preferential shift to fructose metabolism occurs in other species and biological systems as a means to provide fuel, water or like in the naked mole-rat, protection in a low oxygen environment. We review fructose metabolism through an ecological lens and suggest that the metabolic adaptation to utilize fructose in the naked mole-rat may have evolved to simultaneously combat multiple challenges posed by its hostile environment