ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2019
Glycogen Synthase Kinase 3 Beta Controls Presenilin-1-Mediated Endoplasmic Reticulum Ca²⁺ Leak Directed to Mitochondria in Pancreatic Islets and β-Cells.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Presenilin-1 controls glycolysis and identity of pancreatic beta cells.Communications biology · 2026Article
- Review
- Disrupted Endoplasmic Reticulum CaBiology · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- The Dynamics of Calcium Signaling in Beta Cells-A Discussion on the Comparison of Experimental and Modelling Data.International journal of molecular sciences · 2023Article
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Dysregulated CaCells · 2022Review
- Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels.Frontiers in endocrinology · 2022Article
- Sec61 complex/translocon: The role of an atypical ER CaFrontiers in physiology · 2022Review
- Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion.Molecular metabolism · 2021Article
- Balancing ER-Mitochondrial CaTrends in cell biology · 2021Review
- Mitochondrial Calcium Signaling in Pancreatic β-Cell.International journal of molecular sciences · 2021Review
- Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases.Frontiers in cell and developmental biology · 2021Review
- Control by CaCell calcium · 2020Review
- Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity.Science signaling · 2020Article
- A Putative Prohibitin-Calcium Nexus inJournal of diabetes research · 2020Review
- Calcium Signaling in ß-cell Physiology and Pathology: A Revisit.International journal of molecular sciences · 2019Review
- Tracking intra- and inter-organelle signaling of mitochondria.The FEBS journal · 2019Review
- IRE1α modulates ER and mitochondria crosstalk.Nature cell biology · 2019Article
- Mitochondrial-Endoplasmic Reticulum Interplay: A Lifelong On-Off Relationship?Contact (Thousand Oaks (Ventura County, Calif.)) · 2019Article
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14 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsIn pancreatic β-cells, the intracellular Ca²⁺ homeostasis is an essential regulator of the cells major functions. The endoplasmic reticulum (ER) as interactive intracellular Ca²⁺ store balances cellular Ca²⁺. In this study basal ER Ca²⁺ homeostasis was evaluated in order to reveal potential β-cell-specificity of ER Ca²⁺ handling and its consequences for mitochondrial Ca²⁺, ATP and respiration.
methodsThe two pancreatic cell lines INS-1 and MIN-6, freshly isolated pancreatic islets, and the two non-pancreatic cell lines HeLA and EA.hy926 were used. Cytosolic, ER and mitochondrial Ca²⁺ and ATP measurements were performed using single cell fluorescence microscopy and respective (genetically-encoded) sensors/dyes. Mitochondrial respiration was monitored by respirometry. GSK3β activity was measured with ELISA.
resultsAn atypical ER Ca²⁺ leak was observed exclusively in pancreatic islets and β-cells. This continuous ER Ca²⁺ efflux is directed to mitochondria and increases basal respiration and organellar ATP levels, is established by GSK3β-mediated phosphorylation of presenilin-1, and is prevented by either knockdown of presenilin-1 or an inhibition/knockdown of GSK3β. Expression of a presenlin-1 mutant that mimics GSK3β-mediated phosphorylation established a β-cell-like ER Ca²⁺ leak in HeLa and EA.hy926 cells. The ER Ca²⁺ loss in β-cells was compensated at steady state by Ca²⁺ entry that is linked to the activity of TRPC3.
conclusionPancreatic β-cells establish a cell-specific ER Ca²⁺ leak that is under the control of GSK3β and directed to mitochondria, thus, reflecting a cell-specific intracellular Ca²⁺ handling for basal mitochondrial activity.
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