Hexosamine pathway and (ER) protein quality control
Highlights•Hexosamine pathway metabolites are substrates for distinct types of
glycosylation.•Hexosamine pathway activation improves protein quality control.•Diverse
glycosylation mechanisms might affect protein homeostasis.•Are metabolic pathways
involved in stress responses that affect ageing?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 …
glycosylation.•Hexosamine pathway activation improves protein quality control.•Diverse
glycosylation mechanisms might affect protein homeostasis.•Are metabolic pathways
involved in stress responses that affect ageing?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 …
Highlights
- Hexosamine pathway metabolites are substrates for distinct types of glycosylation.
- Hexosamine pathway activation improves protein quality control.
- Diverse glycosylation mechanisms might affect protein homeostasis.
- Are metabolic pathways involved in stress responses that affect ageing?
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.
Elsevier
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