How naked mole rats survive oxygen deprivation

Naked mole rats are famous for their lovable ugliness, their extremely long lives, their ability to evade cancer, and now, too, their capacity to survive without oxygen for 18 minutes. This suffocating experience would kill a mouse—a mammal of similar size, albeit with significantly more hair. According to a new study, the naked mole rat manages the feat by altering its metabolism (Science 2017, DOI: 10.1126/science.aan1505).

Naked mole rats are both social and subterranean: The population in one of their underground colonies can surge to nearly 300 members. As a result, the air in these confined, packed spaces is often low in oxygen and high in carbon dioxide.

To survive these conditions, naked mole rats switch to fueling their energy-producing glycolysis pathways with fructose instead of glucose, explains Gary R. Lewin of the Max Delbrück Center for Molecular Medicine, who led the research with postdoc Jane Reznick and Thomas J. Park of the University of Illinois, Chicago.

For other mammals, low oxygen conditions trigger a shutdown of glycolysis. Without this metabolic pathway, cells can’t produce adenosine triphosphate (ATP), a chemical unit of energy currency. No ATP means that cells eventually run out of energy and die, killing the organism in the process.

Naked mole rats manage to avoid total glycolysis shutdown and death by pumping fructose into their cells during oxygen crises. Fructose feeds into the glycolysis pathway by bypassing a regulatory step that typically shuts down the ATP-making process in low-oxygen conditions.

“Like a cab driver taking a back-road detour around stopped traffic, this rewiring of metabolism permits continued flux through glycolysis,” explain University of Nebraska, Lincoln’s Jay F. Storz and McMaster University’s Grant B. McClelland in a commentary associated with the study (Science 2017, DOI: 10.1126/science.aab3896). “Because every aspect of naked mole rat biology seems to be unusual and bizarre in some way,” the scientists add, “it is perhaps not surprising that they have evolved a particular means of tolerating low oxygen conditions.”