dc.contributor.authorHebbar, Sarita
dc.contributor.authorSahoo, Ishtapran
dc.contributor.authorMatysik, Artur
dc.contributor.authorGarcia, Irene Argudo
dc.contributor.authorOsborne, Kathleen Amy
dc.contributor.authorPapan, Cyrus
dc.contributor.authorTorta, Federico
dc.contributor.authorNarayanaswamy, Pradeep
dc.contributor.authorFun, Xiu Hui
dc.contributor.authorWenk, Markus R
dc.contributor.authorShevchenko, Andrej
dc.contributor.authorSchwudke, Dominik
dc.contributor.authorKraut, Rachel
dc.identifier.citationHebbar, S., Sahoo, I., Matysik, A., Garcia, I. A., Osborne, K. A., Papan, C., et al. (2015). Ceramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutants. Scientific Reports, 5, 15926-.en_US
dc.description.abstractSphingolipid metabolites are involved in the regulation of autophagy, a degradative recycling process that is required to prevent neuronal degeneration. Drosophila blue cheese mutants neurodegenerate due to perturbations in autophagic flux, and consequent accumulation of ubiquitinated aggregates. Here, we demonstrate that blue cheese mutant brains exhibit an elevation in total ceramide levels; surprisingly, however, degeneration is ameliorated when the pool of available ceramides is further increased, and exacerbated when ceramide levels are decreased by altering sphingolipid catabolism or blocking de novo synthesis. Exogenous ceramide is seen to accumulate in autophagosomes, which are fewer in number and show less efficient clearance in blue cheese mutant neurons. Sphingolipid metabolism is also shifted away from salvage toward de novo pathways, while pro-growth Akt and MAP pathways are down-regulated, and ER stress is increased. All these defects are reversed under genetic rescue conditions that increase ceramide generation from salvage pathways. This constellation of effects suggests a possible mechanism whereby the observed deficit in a potentially ceramide-releasing autophagic pathway impedes survival signaling and exacerbates neuronal death.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent18 p.en_US
dc.relation.ispartofseriesScientific Reportsen_US
dc.rights© 2015 Hebbar, S. et al. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBiological Sciences
dc.titleCeramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutantsen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US

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