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Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.ORCID iD: 0000-0002-9310-1876
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2019 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 132, no 9, article id jcs228544Article in journal (Refereed) Published
Abstract [en]

Mitochondria play an essential role in regulating insulin secretion from beta cells by providing the ATP needed for the membrane depolarization that results in voltage-dependent Ca2+ influx and subsequent insulin granule exocytosis. Ca2+, in turn, is also rapidly taken up by the mitochondria and exerts important feedback regulation of metabolism. The aim of this study was to determine whether the distribution of mitochondria within beta cells is important for the secretory capacity of these cells. We find that cortically localized mitochondria are abundant in rodent beta cells, and that these mitochondria redistribute towards the cell interior following depolarization. The redistribution requires Ca2+-induced remodeling of the cortical F-actin network. Using light-regulated motor proteins, we increased the cortical density of mitochondria twofold and found that this blunted the voltage-dependent increase in cytosolic Ca2+ concentration and suppressed insulin secretion. The activity-dependent changes in mitochondria distribution are likely to be important for the generation of Ca2+ microdomains required for efficient insulin granule release.

Place, publisher, year, edition, pages
COMPANY BIOLOGISTS LTD , 2019. Vol. 132, no 9, article id jcs228544
Keywords [en]
Ca2+, Optogenetics, F-actin, Exocytosis, Mitochondria, Insulin
National Category
Cell Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-386181DOI: 10.1242/jcs.228544ISI: 000468130600013PubMedID: 30926624OAI: oai:DiVA.org:uu-386181DiVA, id: diva2:1327143
Funder
Swedish Research Council, MH2015-03087Göran Gustafsson Foundation for Research in Natural Sciences and MedicineÅke Wiberg Foundation, M17-0048Novo Nordisk, NNF15OC0016100EXODIAB - Excellence of Diabetes Research in SwedenAvailable from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved

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Griesche, NadineSanchez, GonzaloIdevall Hagren, Olof

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