title: Hexosamine pathway and (ER) protein quality control.
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.
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Denzel
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany; Department of Molecular and Cellular Biology, Huffington Center on Aging Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany. Electronic address: Antebi@age.mpg.de.
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000378:metabolism; D006031:Glycosylation; D006595:Hexosamines / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008136:Longevity; D011506:Proteins / Q000378:metabolism*; D013312:Stress, Physiological; D056811:Unfolded Protein Response; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
chemical_list: D006595:Hexosamines; D011506:Proteins; D014537:Uridine Diphosphate N-Acetylglucosamine; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)