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Hexosamine pathway and (ER) protein quality control

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Denzel,  M. S.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Antebi,  A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Citation

Denzel, M. S., & Antebi, A. (2014). Hexosamine pathway and (ER) protein quality control. Curr Opin Cell Biol, 33, 14-8. doi:10.1016/j.ceb.2014.10.001.


Cite as: https://hdl.handle.net/21.11116/0000-000B-A354-E
Abstract
Aminosugars produced in the hexosamine pathway (HP) are utilized in protein glycosylation reactions involved in protein maturation and cellular signaling. Recent evidence revealed a role of the HP in protein quality control and ageing. Elevation of the HP product UDP-N-acetylglucosamine in the nematode Caenorhabditis elegans results in resistance towards toxic aggregation-prone proteins, and extended lifespan. Glutamine-fructose 6 phosphate aminotransferase (GFAT-1), the HP's key enzyme, is a target of the unfolded protein response (UPR). Thus, cardiac stress in mice results in GFAT-1 activation that triggers a cytoprotective response. Feeding of glucosamine to aged mice increases their life expectancy. Here we discuss HP activation and cellular protein quality control mechanisms that result in stress resistance and suppression of age-related proteotoxicity.