Journal article
Insulin secretory granules control autophagy in pancreatic β cells
Science (American Association for the Advancement of Science), Vol.347(6224), pp.878-882
02/20/2015
DOI: 10.1126/science.aaa2628
PMID: 25700520
Abstract
Pancreatic beta cells lower insulin release in response to nutrient depletion. The question of whether starved beta cells induce macroautophagy, a predominant mechanism maintaining energy homeostasis, remains poorly explored. We found that, in contrast to many mammalian cells, macroautophagy in pancreatic beta cells was suppressed upon starvation. Instead, starved beta cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D (PKD), a key player in secretory granule biogenesis. Starvation-induced nascent granule degradation triggered lysosomal recruitment and activation of mechanistic target of rapamycin that suppressed macroautophagy. Switching from macroautophagy to insulin granule degradation was important to keep insulin secretion low upon fasting. Thus, beta cells use a PKD-dependent mechanism to adapt to nutrient availability and couple autophagy flux to secretory function.
Details
- Title: Subtitle
- Insulin secretory granules control autophagy in pancreatic β cells
- Creators
- Alexander Goginashvili - Centre National de la Recherche ScientifiqueZhirong Zhang - Université de StrasbourgEric Erbs - Centre National de la Recherche ScientifiqueCoralie Spiegelhalter - Centre National de la Recherche ScientifiquePascal Kessler - Université de StrasbourgMichael Mihlan - Centre National de la Recherche ScientifiqueAdrien Pasquier - Université de StrasbourgKsenia Krupina - Université de StrasbourgNicole Schieber - European Molecular Biology LaboratoryLaura Cinque - Dulbecco Telethon InstituteJoelle Morvan - Centre National de la Recherche ScientifiqueIzabela Sumara - Université de StrasbourgYannick Schwab - European Molecular Biology LaboratoryCarmine Settembre - Federico II University HospitalRomeo Ricci - Centre National de la Recherche Scientifique
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.347(6224), pp.878-882
- DOI
- 10.1126/science.aaa2628
- PMID
- 25700520
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 5
- Grant note
- IGBMC Ph.D. fellowship Bourse Regionale de Recherche from region Alsace; Region Grand-Est European Foundation for the Study of Diabetes/Lilly European Diabetes Research Programme grant Action Thematique et Incitative sur Programme (ATIP)-Avenir program Telethon Grant; Fondazione Telethon INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm) Deutsche Forschungsgemeinschaft; German Research Foundation (DFG) 281271-STRESSMETABOL / European Research Council (ERC) starting grant (ERC-StG); European Research Council (ERC) ERC grant; European Research Council (ERC) EMBL
- Language
- English
- Date published
- 02/20/2015
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9985134037902771
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