ArticleThe Journal of biological chemistry2015
Essential role of mitochondrial Ca2+ uniporter in the generation of mitochondrial pH gradient and metabolism-secretion coupling in insulin-releasing cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 69 citations in OpenAlex.
- Mitochondrial calcium modulates odor-mediated behavioral plasticity in Caenorhabditis elegans.Molecules and cells · 2026Article
- Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.International journal of molecular sciences · 2025Review
- CaBiomedicines · 2023Review
- CaCells · 2022Review
- Emerging role of LETM1/GRP78 axis in lung cancer.Cell death & disease · 2022Article
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Mitochondria-Endoplasmic Reticulum Interplay Regulates Exo-Cytosis in Human Neuroblastoma Cells.Cells · 2022Article
- Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion.Molecular metabolism · 2021Article
- Mitochondrial ion channels in pancreatic β-cells: Novel pharmacological targets for the treatment of Type 2 diabetes.British journal of pharmacology · 2021Review
- Mitochondrial Calcium Signaling in Pancreatic β-Cell.International journal of molecular sciences · 2021Review
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling.Frontiers in physiology · 2021Review
- CaStem cell research & therapy · 2020Article
- Why don't mice lacking the mitochondrial CaThe Journal of physiology · 2020Review
- Targeting Mitochondrial Calcium Uptake with the Natural Flavonol Kaempferol, to Promote Metabolism/Secretion Coupling in Pancreatic β-cells.Nutrients · 2020Article
- Mitochondrial CaMolecules and cells · 2020Article
- Factors Influencing Mitochondrial Function as a Key Mediator of Glucose-Induced Insulin Release: Highlighting Nicotinamide Nucleotide Transhydrogenase.International journal of molecular and cellular medicine · 2020Review
- Article
- The zinc transporter Zip14 (SLC39a14) affects Beta-cell Function: Proteomics, Gene expression, and Insulin secretion studies in INS-1E cells.Scientific reports · 2019Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In pancreatic β-cells, ATP acts as a signaling molecule initiating plasma membrane electrical activity linked to Ca(2+) influx, which triggers insulin exocytosis. The mitochondrial Ca(2+) uniporter (MCU) mediates Ca(2+) uptake into the organelle, where energy metabolism is further stimulated for sustained second phase insulin secretion. Here, we have studied the contribution of the MCU to the regulation of oxidative phosphorylation and metabolism-secretion coupling in intact and permeabilized clonal β-cells as well as rat pancreatic islets. Knockdown of MCU with siRNA transfection blunted matrix Ca(2+) rises, decreased nutrient-stimulated ATP production as well as insulin secretion. Furthermore, MCU knockdown lowered the expression of respiratory chain complexes, mitochondrial metabolic activity, and oxygen consumption. The pH gradient formed across the inner mitochondrial membrane following nutrient stimulation was markedly lowered in MCU-silenced cells. In contrast, nutrient-induced hyperpolarization of the electrical gradient was not altered. In permeabilized cells, knockdown of MCU ablated matrix acidification in response to extramitochondrial Ca(2+). Suppression of the putative Ca(2+)/H(+) antiporter leucine zipper-EF hand-containing transmembrane protein 1 (LETM1) also abolished Ca(2+)-induced matrix acidification. These results demonstrate that MCU-mediated Ca(2+) uptake is essential to establish a nutrient-induced mitochondrial pH gradient which is critical for sustained ATP synthesis and metabolism-secretion coupling in insulin-releasing cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.