ArticleCell chemical biology2016
Structural Insights into Mitochondrial Calcium Uniporter Regulation by Divalent Cations.
Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Centipede Venom Peptides Acting on Ion Channels.Toxins · 2020Pooled it
- Prohibitin controls MRS2-Mediated mitochondrial MgCell reports · 2026Article
- Mechanistic Modeling of MCUx Gatekeeping, CaAmerican journal of physiology. Cell physiology · 2026Article
- Mechanistic basis of EMRE's essential role in the regulation of mitochondrial calcium uniporter complex.bioRxiv : the preprint server for biology · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Mitochondrial CaCommunications biology · 2026Article
- Targeting magnesium homeostasis: a novel therapeutic strategy for liver diseases.Frontiers in nutrition · 2026Review
- Berberine is a Novel Mitochondrial Calcium Uniporter Inhibitor that Disrupts MCU-EMRE Assembly.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ROS-DRP1-mediated excessive mitochondrial fission and autophagic flux inhibition contribute to heat stress-induced apoptosis in goat Sertoli cells.Journal of animal science and biotechnology · 2025Article
- Mechanism of MCUB-Dependent Inhibition of Mitochondrial Calcium Uptake.Journal of cellular physiology · 2025Article
- MCU complex: Exploring emerging targets and mechanisms of mitochondrial physiology and pathology.Journal of advanced research · 2025Review
- Disrupting the network of co-evolving amino terminal domain residues relieves mitochondrial calcium uptake inhibition by MCUb.Computational and structural biotechnology journal · 2025Article
- Metabolic-stress-induced mitochondrial calcium dysregulation: a central hub in diabetic cardiomyopathy pathogenesis and treatment.Frontiers in endocrinology · 2025Review
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- MRS2 missense variation at Asp216 abrogates inhibitory MgProtein science : a publication of the Protein Society · 2024Article
- Article
- Mrs2-mediated mitochondrial magnesium uptake is essential for the regulation of MCU-mediated mitochondrial CaMitochondrion · 2024Article
- Magnesium (MgCurrent pharmaceutical design · 2024Review
- A mitochondrial inside-out iron-calcium signal reveals drug targets for Parkinson's disease.Cell reports · 2023Article
2 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
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Calcium (Ca(2+)) flux into the matrix is tightly controlled by the mitochondrial Ca(2+) uniporter (MCU) due to vital roles in cell death and bioenergetics. However, the precise atomic mechanisms of MCU regulation remain unclear. Here, we solved the crystal structure of the N-terminal matrix domain of human MCU, revealing a β-grasp-like fold with a cluster of negatively charged residues that interacts with divalent cations. Binding of Ca(2+) or Mg(2+) destabilizes and shifts the self-association equilibrium of the domain toward monomer. Mutational disruption of the acidic face weakens oligomerization of the isolated matrix domain and full-length human protein similar to cation binding and markedly decreases MCU activity. Moreover, mitochondrial Mg(2+) loading or blockade of mitochondrial Ca(2+) extrusion suppresses MCU Ca(2+)-uptake rates. Collectively, our data reveal that the β-grasp-like matrix region harbors an MCU-regulating acidic patch that inhibits human MCU activity in response to Mg(2+) and Ca(2+) binding.
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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.