Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

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• dc.contributor.author Hebbara, Sarita
• dc.contributor.author Khandelwal, Avinash
• dc.contributor.author Khandelwal, Avinash, 1987-
• dc.contributor.author Jayashreeb, Rangareddy
• dc.contributor.author Hindlec, Samantha J.
• dc.contributor.author Chiangd, Yin Ning
• dc.contributor.author Yewe, Joanne Y.
• dc.contributor.author Sweeneyc, Sean T.
• dc.contributor.author Schwudke, Dominik
• dc.date.accessioned 2024-01-22T06:50:08Z
• dc.date.available 2024-01-22T06:50:08Z
• dc.date.issued 2017
• dc.description.abstract Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hebbar S, Khandelwal A, Jayashree R, Hindle SJ, Chiang YN, Yew JY, et al. Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders. Molecular Biology of the Cell. 2017 Dec 15;28(26):3728-40. DOI: 10.1091/mbc.e16-09-0674
• dc.identifier.doi http://dx.doi.org/10.1091/mbc.e16-09-0674
• dc.identifier.issn 3727-3895
• dc.identifier.uri http://hdl.handle.net/10230/58775
• dc.language.iso eng
• dc.publisher American Society for Cell Biology
• dc.relation.ispartof Molecular Biology of the Cell. 2017 Dec 15;28(26):3728-40
• dc.rights © 2017 Hebbar et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0
• dc.subject.other Lípids
• dc.subject.other Mutació (Biologia)
• dc.subject.other Metabolisme
• dc.title Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion