| Autor: |
Christiane, Klec, Corina T, Madreiter-Sokolowski, Sarah, Stryeck, Vinay, Sachdev, Madalina, Duta-Mare, Benjamin, Gottschalk, Maria R, Depaoli, Rene, Rost, Jesse, Hay, Markus, Waldeck-Weiermair, Dagmar, Kratky, Tobias, Madl, Roland, Malli, Wolfgang F, Graier |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology |
| ISSN: |
1421-9778 |
| Popis: |
Background/Aims In 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. Methods The 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. Results An 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. Conclusion Pancreatic 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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