ArticleThe Journal of biological chemistry2012
Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) contribute to metabolism-secretion coupling in clonal pancreatic β-cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 136 citations in OpenAlex.
- Cholesterol induced-mitochondrial calcium dysregulation facilitates atherosclerosis by promoting lipid accumulation in vascular smooth muscle cells.Molecular biomedicine · 2025Article
- Integration of signal transduction pathways in sensory epithelial enteroendocrine cells.Molecular biology of the cell · 2025Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- AnPlant signaling & behavior · 2023Article
- Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules · 2023Review
- A Defect in Mitochondrial Complex III but Not in Complexes I or IV Causes Early β-Cell Dysfunction and Hyperglycemia in Mice.Diabetes · 2023Article
- The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.Biomolecules · 2023Review
- CaBiomedicines · 2023Review
- Hepatitis C virus replication requires integrity of mitochondria-associated ER membranes.JHEP reports : innovation in hepatology · 2023Article
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- CaCells · 2022Review
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Review
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance.Science advances · 2021Article
- 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
- Molecular nature and physiological role of the mitochondrial calcium uniporter channel.American journal of physiology. Cell physiology · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
In pancreatic β-cells, uptake of Ca(2+) into mitochondria facilitates metabolism-secretion coupling by activation of various matrix enzymes, thus facilitating ATP generation by oxidative phosphorylation and, in turn, augmenting insulin release. We employed an siRNA-based approach to evaluate the individual contribution of four proteins that were recently described to be engaged in mitochondrial Ca(2+) sequestration in clonal INS-1 832/13 pancreatic β-cells: the mitochondrial Ca(2+) uptake 1 (MICU1), mitochondrial Ca(2+) uniporter (MCU), uncoupling protein 2 (UCP2), and leucine zipper EF-hand-containing transmembrane protein 1 (LETM1). Using a FRET-based genetically encoded Ca(2+) sensor targeted to mitochondria, we show that a transient knockdown of MICU1 or MCU diminished mitochondrial Ca(2+) uptake upon both intracellular Ca(2+) release and Ca(2+) entry via L-type channels. In contrast, knockdown of UCP2 and LETM1 exclusively reduced mitochondrial Ca(2+) uptake in response to either intracellular Ca(2+) release or Ca(2+) entry, respectively. Therefore, we further investigated the role of MICU1 and MCU in metabolism-secretion coupling. Diminution of MICU1 or MCU reduced mitochondrial Ca(2+) uptake in response to d-glucose, whereas d-glucose-triggered cytosolic Ca(2+) oscillations remained unaffected. Moreover, d-glucose-evoked increases in cytosolic ATP and d-glucose-stimulated insulin secretion were diminished in MICU1- or MCU-silenced cells. Our data highlight the crucial role of MICU1 and MCU in mitochondrial Ca(2+) uptake in pancreatic β-cells and their involvement in the positive feedback required for sustained insulin secretion.
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Registered trials
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.