Universität zu Köln

Denzel, Martin S., Storm, Nadia J., Gutschmidt, Aljona, Baddi, Ruth, Hinze, Yvonne, Jarosch, Ernst ORCID: 0000-0002-5897-3492, Sommer, Thomas, Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Antebi, Adam (2014). Hexosamine Pathway Metabolites Enhance Protein Quality Control and Prolong Life. Cell, 156 (6). S. 1167 - 1179. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

Full text not available from this repository.

Abstract

Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here, we report that increased synthesis of N-glycan precursors in the hexosamine pathway improves ER protein homeostasis and extends lifespan in C. elegans. Addition of the N-glycan precursor N-acetylglucosamine to the growth medium slows aging in wild-type animals and alleviates pathology of distinct neurotoxic disease models. Our data suggest that reduced aggregation of metastable proteins and lifespan extension depend on enhanced ER-associated protein degradation, proteasomal activity, and autophagy. Evidently, hexosamine pathway activation or N-acetylglucosamine supplementation induces distinct protein quality control mechanisms, which may allow therapeutic intervention against age-related and proteotoxic diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Denzel, Martin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Storm, Nadia J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutschmidt, Aljona UNSPECIFIED UNSPECIFIED UNSPECIFIED Baddi, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinze, Yvonne UNSPECIFIED UNSPECIFIED UNSPECIFIED Jarosch, Ernst UNSPECIFIED orcid.org/0000-0002-5897-3492 UNSPECIFIED Sommer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443410
DOI:	10.1016/j.cell.2014.01.061
Journal or Publication Title:	Cell
Volume:	156
Number:	6
Page Range:	S. 1167 - 1179
Date:	2014
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOPLASMIC-RETICULUM STRESS; TRANSGENIC CAENORHABDITIS-ELEGANS; HEAT-SHOCK FACTOR; C. ELEGANS; AUTOPHAGY GENES; LONGEVITY; ER; DEGRADATION; DISEASE; SPAN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/44341