Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep15926
Title: Ceramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutants
Authors: Hebbar, Sarita
Sahoo, Ishtapran
Matysik, Artur
Garcia, Irene Argudo
Osborne, Kathleen Amy
Papan, Cyrus
Torta, Federico 
Narayanaswamy, Pradeep 
Fun, Xiu Hui
Wenk, Markus R 
Shevchenko, Andrej
Schwudke, Dominik
Kraut, Rachel
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NOVO SPHINGOLIPID BIOSYNTHESIS
TANDEM MASS-SPECTROMETRY
AMYLOID-BETA
PROTEIN
CHOLESTEROL
METABOLISM
APOPTOSIS
PATHWAY
CHROMATOGRAPHY
DISSOCIATION
Issue Date: 7-Dec-2015
Publisher: NATURE PUBLISHING GROUP
Citation: Hebbar, Sarita, Sahoo, Ishtapran, Matysik, Artur, Garcia, Irene Argudo, Osborne, Kathleen Amy, Papan, Cyrus, Torta, Federico, Narayanaswamy, Pradeep, Fun, Xiu Hui, Wenk, Markus R, Shevchenko, Andrej, Schwudke, Dominik, Kraut, Rachel (2015-12-07). Ceramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutants. SCIENTIFIC REPORTS 5 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/srep15926
Abstract: Sphingolipid 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.
Source Title: SCIENTIFIC REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/170372
ISSN: 20452322
DOI: 10.1038/srep15926
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
68. Ceramides And Stress Signalling Intersect With Autophagic Defects.pdfPublished version3.04 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

12
checked on Sep 13, 2020

Page view(s)

32
checked on Sep 17, 2020

Download(s)

1
checked on Sep 17, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.