ArticlePloS one2012
The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic β-cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Knowledge mapping of mitochondrial calcium uniporter from 2011 to 2022: A bibliometric analysis.Frontiers in physiology · 2023Pooled it
- Mitochondria-Endoplasmic Reticulum Crosstalk in Pancreatic β-Cell Stress: A Driver of Diabetes.Cells · 2026Review
- Mitochondrial calcium influx-driven bioenergetics selectively enable drug addiction.Nature neuroscience · 2026Article
- Mitochondrial position responds to glucose stimulation in a model of the pancreatic beta cell.Biophysical journal · 2026Article
- Review
- Mitochondrial CaJournal of cellular physiology · 2025Review
- Primary Hyperparathyroidism: An Analysis Amid the Co-Occurrence of Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2025Review
- Article
- Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells.Diabetes · 2025Article
- Metabolic-stress-induced mitochondrial calcium dysregulation: a central hub in diabetic cardiomyopathy pathogenesis and treatment.Frontiers in endocrinology · 2025Review
- Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop.PLoS computational biology · 2024Article
- Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- A primer on modelling pancreatic islets: from models of coupled β-cells to multicellular islet models.Islets · 2023Review
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.Biomolecules · 2023Review
- Simultaneous Measurement of Changes in Mitochondrial and Endoplasmic Reticulum Free Calcium in Pancreatic Beta Cells.Biosensors · 2023Article
- CaCells · 2022Review
- Opposing effects on regulated insulin secretion of acute vs chronic stimulation of AMP-activated protein kinase.Diabetologia · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
Abstract
Glucose induces insulin release from pancreatic β-cells by stimulating ATP synthesis, membrane depolarisation and Ca(2+) influx. As well as activating ATP-consuming processes, cytosolic Ca(2+) increases may also potentiate mitochondrial ATP synthesis. Until recently, the ability to study the role of mitochondrial Ca(2+) transport in glucose-stimulated insulin secretion has been hindered by the absence of suitable approaches either to suppress Ca(2+) uptake into these organelles, or to examine the impact on β-cell excitability. Here, we have combined patch-clamp electrophysiology with simultaneous real-time imaging of compartmentalised changes in Ca(2+) and ATP/ADP ratio in single primary mouse β-cells, using recombinant targeted (Pericam or Perceval, respectively) as well as entrapped intracellular (Fura-Red), probes. Through shRNA-mediated silencing we show that the recently-identified mitochondrial Ca(2+) uniporter, MCU, is required for depolarisation-induced mitochondrial Ca(2+) increases, and for a sustained increase in cytosolic ATP/ADP ratio. By contrast, silencing of the mitochondrial Na(+)-Ca(2+) exchanger NCLX affected the kinetics of glucose-induced changes in, but not steady state values of, cytosolic ATP/ADP. Exposure to gluco-lipotoxic conditions delayed both mitochondrial Ca(2+) uptake and cytosolic ATP/ADP ratio increases without affecting the expression of either gene. Mitochondrial Ca(2+) accumulation, mediated by MCU and modulated by NCLX, is thus required for normal glucose sensing by pancreatic β-cells, and becomes defective in conditions mimicking the diabetic milieu.
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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.