Targeting surface voids to counter membrane disorders in lipointoxication-related diseases.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620456
Title:
Targeting surface voids to counter membrane disorders in lipointoxication-related diseases.
Authors:
Ferru-Clément, R.; Spanova, M.; Dhayal, S.; Morgan, Noel; Hélye, R.; Becq, F.; Hirose, H.; Antonny, B.; Vamparys, L.; Fuchs, P. F. J.; Ferreira, T.
Abstract:
Saturated fatty acids (SFA), which are abundant in the so-called western diet, have been shown to efficiently incorporate within membrane phospholipids and therefore impact on organelle integrity and function in many cell types. In the present study, we have developed a yeast-based two-step assay and a virtual screening strategy to identify new drugs able to counter SFA-mediated lipointoxication. The compounds identified here were effective in relieving lipointoxication in mammalian β-cells, one of the main targets of SFA toxicity in humans. In vitro reconstitutions and molecular dynamics simulations on bilayers revealed that these molecules, albeit according to different mechanisms, can generate voids at the membrane surface. The resulting surface defects correlate with the recruitment of loose lipid packing or void-sensing proteins required for vesicular budding, a central cellular process that is precluded under SFA accumulation. Taken together, the results presented here point at modulation of surface voids as a central parameter to consider in order to counter the impacts of SFA on cell function.
Citation:
Targeting surface voids to counter membrane disorders in lipointoxication-related diseases. 2016, 129 (12):2368-81 J. Cell. Sci.
Publisher:
The Company of Biologists
Journal:
Journal of cell science
Issue Date:
15-Jun-2016
URI:
http://hdl.handle.net/11287/620456
DOI:
10.1242/jcs.183590
PubMed ID:
27142833
Additional Links:
http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=27142833
Note:
This article is freely available from the publisher's site. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
ISSN:
1477-9137
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorFerru-Clément, R.en
dc.contributor.authorSpanova, M.en
dc.contributor.authorDhayal, S.en
dc.contributor.authorMorgan, Noelen
dc.contributor.authorHélye, R.en
dc.contributor.authorBecq, F.en
dc.contributor.authorHirose, H.en
dc.contributor.authorAntonny, B.en
dc.contributor.authorVamparys, L.en
dc.contributor.authorFuchs, P. F. J.en
dc.contributor.authorFerreira, T.en
dc.date.accessioned2017-10-18T14:01:42Z-
dc.date.available2017-10-18T14:01:42Z-
dc.date.issued2016-06-15-
dc.identifier.citationTargeting surface voids to counter membrane disorders in lipointoxication-related diseases. 2016, 129 (12):2368-81 J. Cell. Sci.en
dc.identifier.issn1477-9137-
dc.identifier.pmid27142833-
dc.identifier.doi10.1242/jcs.183590-
dc.identifier.urihttp://hdl.handle.net/11287/620456-
dc.description.abstractSaturated fatty acids (SFA), which are abundant in the so-called western diet, have been shown to efficiently incorporate within membrane phospholipids and therefore impact on organelle integrity and function in many cell types. In the present study, we have developed a yeast-based two-step assay and a virtual screening strategy to identify new drugs able to counter SFA-mediated lipointoxication. The compounds identified here were effective in relieving lipointoxication in mammalian β-cells, one of the main targets of SFA toxicity in humans. In vitro reconstitutions and molecular dynamics simulations on bilayers revealed that these molecules, albeit according to different mechanisms, can generate voids at the membrane surface. The resulting surface defects correlate with the recruitment of loose lipid packing or void-sensing proteins required for vesicular budding, a central cellular process that is precluded under SFA accumulation. Taken together, the results presented here point at modulation of surface voids as a central parameter to consider in order to counter the impacts of SFA on cell function.en
dc.language.isoenen
dc.publisherThe Company of Biologistsen
dc.relation.urlhttp://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=27142833en
dc.rightsArchived with thanks to Journal of cell scienceen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subject.meshCell Membrane-
dc.subject.meshDiglycerides-
dc.subject.meshEndoplasmic Reticulum Stress-
dc.subject.meshLipids-
dc.subject.meshLysophospholipids-
dc.subject.meshMetabolome-
dc.subject.meshMetabolomics-
dc.subject.meshPharmacogenetics-
dc.subject.meshSaccharomyces cerevisiae-
dc.subject.meshSecretory Pathway-
dc.subject.meshTranscriptome-
dc.subject.meshUser-Computer Interface-
dc.titleTargeting surface voids to counter membrane disorders in lipointoxication-related diseases.en
dc.typeJournal Articleen
dc.identifier.journalJournal of cell scienceen
dc.description.noteThis article is freely available from the publisher's site. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden

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