title: Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.
abstract: Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited, despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent system to study this mechanism. We found, through genetic manipulation and lipid analysis, that biosynthesis of ceramide, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic interaction analysis suggests that ceramide may act in both insulin-IGF-1 signaling (IIS)-dependent and IIS-independent pathways to affect starvation survival. Genetic and expression analyses indicate that ceramide is required for maintaining the proper expression of previously characterized starvation-responsive genes, genes that are regulated by the IIS pathway and tumor suppressor Rb, and genes responsive to pathogen. These findings provide an important insight into the roles of sphingolipid metabolism, not only in starvation response, but also in aging and food-response-related human health problems.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309.
authors.forename: Mingxue
authors.initials: M
authors.lastname: Cui
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Cavaleri
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309.
authors.forename: Taylor
authors.initials: T
authors.lastname: Kelson
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular, Cellular and Developmental Biology, University of Colorado at Boulder, Colorado 80309 mhan@colorado.edu.
authors.forename: Min
authors.identifier: 0000-0001-6845-2570
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis* / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D013217:Starvation / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D002518:Ceramides; D007328:Insulin; D017526:Receptor, IGF Type 1
keywords: Rb; daf-16; hyl-1; pathogen; serine palmitoyltransferase