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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2015 (arch)     Display Documents



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ID: 718046.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2015 (arch)
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
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Scientific Reports
Volume:5
Sequence Number of Article:15926
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6407
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