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A Sweet Story of Metabolic Innovation in the Naked Mole-Rat

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The Extraordinary Biology of the Naked Mole-Rat

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1319))

Abstract

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.

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Photo Credit: Gary R. Lewin

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Acknowledgements

The work in the authors laboratories has been supported by the following agencies: ERC advanced grants to GRL (AdG 789128 and AdG 294678), and a National Science Foundation grant to TJP (1655494).

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Authors and Affiliations

  1. Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

    Jane Reznick

  2. Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

  3. Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin

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  1. Jane Reznick
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Correspondence to Jane Reznick .

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Editors and Affiliations

  1. Calico Life Sciences LLC, South San Francisco, CA, USA

    Rochelle Buffenstein

  2. Laboratory of Integrative NeuroscienceDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

  3. Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada

    Melissa M. Holmes

Glossary

Glycolysis:

A metabolic process that occurs in almost all living cells in which glucose is converted in a series of steps to pyruvic acid and during which energy is released in the form of ATP.

Fructose:

A very sweet simple sugar (monosaccharide), C6H12O6 occurring in many fruits and in honey.

Sucrose:

A nonreducing disaccharide from sugar cane. Sucrose (C12H22O11) is formed by a condensation reaction between fructose and glucose and can be broken down by acid hydrolysis or incubation with the enzyme sucrase.

Insulin resistance:

Insulin resistance is a state or condition in which tissues in the body have a lowered level of response to insulin, a hormone secreted by the pancreas that helps to regulate the level of glucose in the body.

Hypoxia:

Lower than normal levels of oxygen in inspired gases, arterial blood, or tissues.

Anoxia:

A condition characterized by an absence of oxygen supply to an organ or a tissue.

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Reznick, J., Park, T.J., Lewin, G.R. (2021). A Sweet Story of Metabolic Innovation in the Naked Mole-Rat. In: Buffenstein, R., Park, T.J., Holmes, M.M. (eds) The Extraordinary Biology of the Naked Mole-Rat. Advances in Experimental Medicine and Biology, vol 1319. Springer, Cham. https://doi.org/10.1007/978-3-030-65943-1_10

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