Welcome to the UPF Digital Repository

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

Show simple item record

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.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.issn 3727-3895
dc.identifier.uri http://hdl.handle.net/10230/58775
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.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.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.identifier.doi http://dx.doi.org/10.1091/mbc.e16-09-0674
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

In collaboration with Compliant to Partaking