Lipid metabolic perturbation is an early-onset phenotype in adultmutants: amodel for lysosomal storage disorders. [Lipidomics Facility]

You are here

TitleLipid metabolic perturbation is an early-onset phenotype in adultmutants: amodel for lysosomal storage disorders. [Lipidomics Facility]
Publication TypeJournal Article
Year of Publication2017
AuthorsHebbar S, Khandelwal A, Jayashree R, Hindle SJ, Chiang YNing, Yew JY, Sweeney ST, Schwudke D
JournalMol Biol Cell
Volume28
Issue26
Pagination3728-3740
Date Published2017 Dec 15
ISSN1939-4586
KeywordsAnimals, Carrier Proteins, Disease Models, Animal, Drosophila, Drosophila Proteins, Lipid Metabolism, Lipids, Lipoproteins, Lysosomal Storage Diseases, Lysosomes, Membrane Proteins, Mutation, Nervous System, Neurodegenerative Diseases, Phenotype
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 inmutants, amodel 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 ofand altering these lipids inmutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral tofunction 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 inmutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes inmutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD.

DOI10.1091/mbc.E16-09-0674
Alternate JournalMol. Biol. Cell
PubMed ID29046397
PubMed Central IDPMC5739291
Grant List / / Wellcome Trust / United Kingdom

Comments

.