دورية أكاديمية
Targeting surface voids to counter membrane disorders in lipointoxication-related diseases.
| العنوان: | Targeting surface voids to counter membrane disorders in lipointoxication-related diseases. |
|---|---|
| المؤلفون: | Ferru-Clément, Romain, Spanova, Miroslava, Dhayal, Shalinee, Morgan, Noel G, Hélye, Reynald, Becq, Frédéric, Hirose, Hisaaki, Antonny, Bruno, Vamparys, Lydie, Fuchs, Patrick F J, Ferreira, Thierry |
| المساهمون: | Signalisation et Transports Ioniques Membranaires (STIM Poitiers ), Université de Poitiers = University of Poitiers (UP)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Société d’accélération du transfert de technologie Grand Centre (SATT Grand Centre), Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter-University of Exeter, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Diabetes UK grant number 12/0004505, Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche (French MENRT), Centre National de la Recherche Scientifique (CNRS), European Foundation for the Study of Diabetes (EFSD), Fonds européen de développement régional (FEDER) |
| المصدر: | ISSN: 0021-9533. |
| بيانات النشر: | HAL CCSD Company of Biologists |
| سنة النشر: | 2016 |
| المجموعة: | HAL Université Côte d'Azur |
| مصطلحات موضوعية: | Early secretory pathway, Lipointoxication, Membrane interfacial surface voids, Type 2 diabetes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27142833; hal-01337179; https://hal.science/hal-01337179Test; PUBMED: 27142833 |
| DOI: | 10.1242/jcs.183590 |
| الإتاحة: | https://doi.org/10.1242/jcs.183590Test https://hal.science/hal-01337179Test |
| رقم الانضمام: | edsbas.F84DFDF3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1242/jcs.183590 |
|---|