Affinage

MCU

Calcium uniporter protein, mitochondrial · UniProt Q8NE86

Length
351 aa
Mass
39.9 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCU (CCDC109A) is the pore-forming subunit of the mitochondrial calcium uniporter, an oligomeric Ca2+-selective channel of the inner mitochondrial membrane that mediates the bulk of mitochondrial Ca2+ entry (PMID:21685886, PMID:23755363). Identified through phylogenetic and co-expression profiling and confirmed by whole-mitoplast electrophysiology, MCU silencing abrogates mitochondrial Ca2+ uptake and the inward mitochondrial Ca2+ current (IMiCa) without affecting respiration or membrane potential, while pore-domain point mutations alter ruthenium red/Ru360 sensitivity, establishing MCU as the channel itself (PMID:21685886, PMID:23755363). The channel is a tetramer with a single ion pore whose conserved DIME selectivity filter conducts Ca2+; functional reconstitution requires the accessory subunit EMRE and cardiolipin (PMID:32841658). Channel gating is governed by the MICU1–MICU2 heterodimer, which is covalently linked by a Mia40/CHCHD4-introduced disulfide bond and binds the DIME D-ring of MCU at low Ca2+ to set a Ca2+ uptake threshold and prevent constitutive loading, then rearranges and modulates flux as cytosolic Ca2+ rises (PMID:23101630, PMID:26387864, PMID:30454562, PMID:30638448, PMID:26489515). Matrix-facing Ca2+ sensing within the MCU N-terminus provides a second, bidirectional layer of regulation that can close the channel even when MICU1/2 are Ca2+-bound (PMID:32801213), and the MICU1:MCU and EMRE:MCU stoichiometries tune the threshold and cooperativity of activation in a tissue-specific manner (PMID:28273446, PMID:32315830). Assembly and abundance of the complex are controlled by the scaffold factor MCUR1, by SPG7-directed m-AAA protease processing of MCU and degradation of unassembled EMRE, and by redox-sensitive S-glutathionylation of Cys-97 that drives higher-order oligomerization and persistent activity (PMID:28262504, PMID:27184846, PMID:27642048, PMID:31097542). MCU expression is transcriptionally tuned by cytosolic Ca2+ acting through CaMKII/CREB to upregulate the gene and through Npas4-mediated repression in neurons (PMID:25737585, PMID:35167328, PMID:23774321). Functionally, MCU-mediated Ca2+ influx drives mitochondrial bioenergetics, redox state, cell-cycle progression and mitochondrial dynamics, glucose-stimulated insulin secretion, and metabolic adaptation, whereas uncontrolled Ca2+ (or Mn2+) entry promotes ROS, mPTP opening, and cell death (PMID:30858581, PMID:31040260, PMID:30403999, PMID:37302345, PMID:32350566).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 High

    Established the molecular identity of the long-sought uniporter pore: before this it was unknown which protein conducts mitochondrial Ca2+, and convergent genomics plus loss-of-function pinned it on MCU.

    Evidence Phylogenetic/co-expression profiling, RNAi in cells and mouse liver, Co-IP with MICU1, topology and mutagenesis

    PMID:21685886

    Open questions at the time
    • Channel oligomeric state and pore architecture not resolved at atomic level
    • EMRE requirement not yet appreciated
  2. 2013 High

    Proved MCU is the channel-forming subunit rather than an accessory protein, by showing knockdown and overexpression scale IMiCa and a pore mutation removes ruthenium red sensitivity without changing current.

    Evidence Whole-mitoplast voltage-clamp electrophysiology with RNAi, overexpression, and pore mutagenesis

    PMID:23755363

    Open questions at the time
    • Does not define the selectivity filter residues
    • No reconstituted minimal channel
  3. 2012 High

    Identified MICU1 as the gatekeeper that sets a Ca2+ threshold, explaining how the channel avoids constitutive matrix Ca2+ loading.

    Evidence Co-IP, siRNA knockdown, mitochondrial Ca2+ imaging and cell death assays

    PMID:23101630

    Open questions at the time
    • Molecular interface with MCU undefined
    • Role of MICU2 unaddressed
  4. 2015 High

    Defined how MICU subunits sense cytosolic Ca2+: a Mia40-linked MICU1–MICU2 disulfide heterodimer binds MCU at low Ca2+ and dissociates at high Ca2+, and EF-hand-driven MICU1 multimer rearrangement (EC50 ~4.4 µM) couples cytosolic Ca2+ to channel activation.

    Evidence Disulfide biochemistry, Mia40 interactome, Co-IP, and live-cell FRET with EF-hand mutants

    PMID:26387864 PMID:26489515

    Open questions at the time
    • Structural basis of the MICU–MCU contact not yet mapped
    • FRET multimer model is single-lab (Medium)
  5. 2016 High

    Showed the complex requires active assembly control: MCUR1 scaffolds MCU–EMRE, and m-AAA protease degrades unassembled EMRE to ensure gatekeeper incorporation, preventing constitutively active channels.

    Evidence Reciprocal Co-IP and domain mapping; m-AAA protease genetic KO with assembly and Ca2+ assays in neurons

    PMID:27184846 PMID:27642048

    Open questions at the time
    • MCUR1 mechanism distinguishing scaffold vs. regulator debated
    • Quantitative subunit stoichiometry unknown
  6. 2017 High

    Revealed redox and stoichiometric control of channel activity: Cys-97 S-glutathionylation drives oligomerization and persistent activity, and the tissue-specific MICU1:MCU ratio tunes threshold and cooperativity.

    Evidence S-glutathionylation assay, superresolution imaging and mutagenesis; quantitative protein ratio and cardiac MICU1 overexpression mouse

    PMID:28262504 PMID:28273446

    Open questions at the time
    • In vivo enzymes catalyzing Cys-97 glutathionylation not identified
    • How ratio is set developmentally unclear
  7. 2018 High

    Localized the gatekeeper interface to the DIME selectivity filter: MICU1's DID engages the DIME D-ring/aspartate to control flux and Ru360 sensitivity, with MICU2 modulating the threshold and gain of MICU1 regulation.

    Evidence Site-directed mutagenesis of MCU DIME and MICU1 DID/Arg residues with Ca2+ uptake, Ru360, and survival assays

    PMID:29241542 PMID:30454562

    Open questions at the time
    • Atomic structure of the assembled human MICU–MCU interface lacking
    • MICU2-only regulation (Medium) single-lab
  8. 2019 High

    Extended the electrostatic MCU–MICU1 model and connected MCU to cell-division energetics: a Ca2+-modulated DIME-Asp/MICU1-Arg contact gates flux, while AMPK phosphorylates MCU during mitosis to drive a respiratory Ca2+ transient.

    Evidence Mutagenesis Ca2+ flux screen; AMPK mitochondrial translocation imaging, phosphorylation, and mitotic Ca2+/ATP measurements with MCU depletion

    PMID:30638448 PMID:30858581

    Open questions at the time
    • MCU phosphosite(s) and kinase specificity in mitosis not fully mapped
    • Generality across cell types untested
  9. 2020 High

    Provided the structural and stoichiometric framework: a tetrameric MCU-EMRE cryo-EM structure with single pore, EMRE/cardiolipin requirements for conduction, and demonstration that matrix Ca2+ sensors in the MCU N-terminus and EMRE:MCU ratio jointly tune gating.

    Evidence Cryo-EM of T. castaneum MCU-EMRE with proteoliposome reconstitution; concatemer stoichiometry and dual-side electrophysiology with mutagenesis

    PMID:32315830 PMID:32801213 PMID:32841658 PMID:33296646

    Open questions at the time
    • No high-resolution structure of the full mammalian MCU–MICU1/2–EMRE–MCUR1 holocomplex
    • Concatemer/stoichiometry studies single-lab (Medium)
  10. 2019 High

    Linked MCU-driven Ca2+ to mitochondrial dynamics, cell-cycle progression, and hepatic metabolism via downstream phosphatase/kinase circuits.

    Evidence MCU genetic deletion with CaMKII/Drp1 fission-fusion analysis; liver-specific MCU deletion with PP4/AMPK signaling and lipid quantification; SPG7-directed MCU processing KO

    PMID:30917323 PMID:31040260 PMID:31097542

    Open questions at the time
    • Directionality of MCU/CaMKII feedback incompletely resolved
    • PP4 and SPG7 roles validated in single labs (Medium)
  11. 2022 High

    Defined transcriptional control of MCU abundance by Ca2+ signaling, integrating store-operated/β-adrenergic Ca2+ entry through CaMKII/CREB activation and Npas4-mediated repression.

    Evidence ChIP and promoter reporters with genetic deletion of IP3R/STIM1/Orai1; cardiac MCU KO/overexpression with β-AR/CaMKIIδB/CREB pathway dissection; neuronal Npas4 repression assays

    PMID:23774321 PMID:25737585 PMID:35167328

    Open questions at the time
    • Full set of MCU promoter regulators across tissues unknown
    • Crosstalk between transcriptional and post-translational control unresolved
  12. 2020 High

    Demonstrated physiological consequences of MCU Ca2+ flux in metabolism: required for glucose-stimulated insulin secretion and embedded in a TCA substrate-availability feedback circuit acting through MICU1.

    Evidence Beta cell-specific Mcu KO with Ca2+/ATP imaging, electrophysiology, and glucose tolerance tests; MPC perturbation with EGR1-driven MICU1 upregulation

    PMID:32317369 PMID:32350566

    Open questions at the time
    • Substrate-feedback circuit (Medium) single-lab
    • Whole-body metabolic integration incompletely defined
  13. 2024 Medium

    Tested whether MCU is the sole route of pathological mitochondrial Ca2+ entry, revealing context dependence: MCU is the only detectable route in heart, yet an MCU-independent uptake mechanism drives mPTP and necrosis in dystrophic muscle.

    Evidence Optical Ca2+ measurement in intact MCU-KO hearts; myofiber-specific Mcu/Mcub deletion in a Duchenne model with Ca2+, histology, and function readouts

    PMID:34686324 PMID:38514795

    Open questions at the time
    • Identity of the MCU-independent uptake pathway unknown
    • Both negative/comparative results are single-lab
  14. 2023 Medium

    Expanded the MCU interactome and disease links: MARS2 (methionine-gated), RIPK1, Miro1, VDAC1, STAT3, HINT2, and Parkin (via MICU1) modulate MCU activity or assembly, and cardiolipin stabilizes MICU1 in Barth syndrome.

    Evidence Co-IP/domain mapping with functional Ca2+ readouts across cancer, ischemia, neuronal transport, and disease models

    PMID:29531160 PMID:29686046 PMID:30242232 PMID:31463567 PMID:34494107 PMID:34914018 PMID:36774778

    Open questions at the time
    • Most interactions rest on single-lab Co-IP without structural or reciprocal validation
    • Direct vs. indirect effects on MCU not always distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of the fully assembled, gated mammalian holocomplex and the molecular identity of the MCU-independent mitochondrial Ca2+ uptake route remain open.
  • No structure of mammalian MCU–MICU1/2–EMRE–MCUR1 in gated states
  • MCU-independent uptake pathway in dystrophic muscle unidentified
  • In vivo enzymes controlling Cys-97 redox and MCU phosphorylation not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140299 molecular sensor activity 2
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1640170 Cell Cycle 2
Partners
EMREMCUR1MICU1MICU2MIRO1RIPK1SLC25A23VDAC1
Complex memberships
mitochondrial calcium uniporter (MCU-EMRE-MICU1/2-MCUR1)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 MCU (CCDC109A) was identified as the pore-forming component of the mitochondrial calcium uniporter. MCU forms oligomers in the mitochondrial inner membrane, physically interacts with MICU1, and resides within a large molecular weight complex. Silencing MCU severely abrogates mitochondrial Ca2+ uptake without affecting respiration or membrane potential. Two predicted transmembrane helices are separated by a conserved linker facing the intermembrane space; acidic residues in this linker are required for full activity, and an S259A mutation confers resistance to Ru360. Whole-genome phylogenetic profiling, genome-wide RNA co-expression, organelle-wide protein co-expression, RNAi silencing in cells and mouse liver, Co-IP, transmembrane topology analysis, site-directed mutagenesis, pharmacological inhibition Nature High 21685886
2013 MCU encodes the pore-forming subunit of the mitochondrial Ca2+ uniporter channel. RNAi-mediated knockdown of MCU reduces mitochondrial Ca2+ current (IMiCa) and overexpression increases it. A point mutation in the putative pore domain abolishes ruthenium red sensitivity without altering current magnitude, establishing MCU as the channel-forming subunit. Whole-mitoplast voltage-clamp electrophysiology, RNAi knockdown, overexpression, site-directed mutagenesis eLife High 23755363
2012 MICU1 interacts with the pore-forming subunit MCU and functions as a gatekeeper that sets a Ca2+ threshold for mitochondrial Ca2+ uptake without affecting MCU kinetic properties. Loss of MICU1 causes constitutive mitochondrial Ca2+ loading, excessive ROS, and apoptotic sensitivity. Co-immunoprecipitation, siRNA knockdown, mitochondrial Ca2+ imaging, cell death assays Cell High 23101630
2017 The conserved Cys-97 in human MCU is the only reactive thiol that undergoes S-glutathionylation under oxidative/inflammatory conditions, acting as a redox sensor. MCU oxidation or Cys-97 mutation promotes higher-order MCU oligomer formation, persistent channel activity, increased mitochondrial Ca2+ uptake, elevated mitochondrial ROS, and enhanced Ca2+ overload-induced cell death, largely independently of MCU interactions with its regulatory subunits. S-glutathionylation biochemical assay, superresolution imaging, site-directed mutagenesis, mitochondrial Ca2+ current measurements, inflammatory and hypoxia cell models Molecular cell High 28262504
2016 MCUR1 functions as a scaffold factor for the MCU complex. MCUR1 binds to both MCU and EMRE; loss of MCUR1 impairs mitochondrial Ca2+ uptake and IMiCa current. The minimal coiled-coil domains of MCU and MCUR1 are necessary for heterooligomeric complex formation. Protein binding assays, Co-IP, IMiCa current measurement, MCUR1 knockout in cardiomyocytes and endothelial cells, domain mapping Cell reports High 27184846
2015 Mia40/CHCHD4 introduces an intermolecular disulfide bond linking MICU1 and MICU2 in a heterodimer. The MICU1-MICU2 heterodimer binds MCU at low Ca2+ concentrations and dissociates upon high Ca2+, providing a Ca2+-dependent mechanism for gating mitochondrial Ca2+ uptake. Mia40 interactome analysis, disulfide bond biochemistry, Co-IP, mitochondrial Ca2+ uptake measurements Cell metabolism High 26387864
2016 The m-AAA protease degrades non-assembled EMRE subunits to ensure efficient assembly of gatekeeper subunits (MICU1/MICU2) with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria, causing mitochondrial Ca2+ overload and neuronal death. Neuronal interactome analysis, genetic knockout of m-AAA protease, MCU complex assembly assays, mitochondrial Ca2+ measurements, cell death assays Molecular cell High 27642048
2018 MICU1 interacts with the D-ring formed by the DIME motif (selectivity filter) of MCU to control Ca2+ flux and gatekeeping. MICU1 suppresses ruthenium red/Ru360 inhibition of MCU; a DIME-interacting domain (DID) in MICU1 is required for both gatekeeping and cooperative activation of MCU as well as cell survival. Site-directed mutagenesis of MCU DIME motif and MICU1 DID, Ca2+ uptake assays, Ru360 inhibition assays, cell survival assays Molecular cell High 30454562
2019 The DIME-aspartate of MCU mediates a Ca2+-modulated electrostatic interaction with MICU1, forming a contact interface with a nearby Ser residue at the cytoplasmic entrance of the MCU pore. Two conserved Arg residues in MICU1 contact the DIME-Asp. Perturbing MCU-MICU1 interactions causes unregulated, constitutive Ca2+ flux into mitochondria. Mutagenesis screen of MCU DIME residues and MICU1 Arg residues, mitochondrial Ca2+ flux assays eLife High 30638448
2020 Cryo-EM structure of an MCU-EMRE complex from Tribolium castaneum at 3.5 Å resolution reveals a tetrameric channel with a single ion pore. EMRE is located at the periphery of the transmembrane domain and associates primarily with the first transmembrane helix of MCU. Ca2+ uptake into proteoliposomes requires both EMRE and cardiolipin. Cryo-EM structure determination, proteoliposome reconstitution Ca2+ uptake assay, lipid dependence assays Journal of molecular biology High 32841658
2020 EMRE controls MCU activity via its transmembrane helix, while an N-terminal PKP motif strengthens MCU binding. MCU opening requires hydrophobic interactions near the pore's luminal end. A single mutation at this site allows human MCU to transport Ca2+ without EMRE. EMRE may facilitate MCU opening by stabilizing the open state in a conserved gating mechanism present in non-metazoan MCU homologs. Site-directed mutagenesis, MCU-EMRE concatemer constructs, Ca2+ uptake assays in cells lacking EMRE/MCU Cell reports High 33296646
2019 AMPK translocates to mitochondria during mitosis and phosphorylates MCU in a mitosis-specific manner, activating a rapid mitochondrial Ca2+ transient during cell division. MCU-mediated mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis during early mitotic ATP drop. Depletion of MCU causes spindle checkpoint-dependent mitotic delay. MCU depletion (RNAi), AMPK mitochondrial translocation imaging, phosphorylation assays, mitochondrial Ca2+ and ATP measurements during mitosis, cell cycle analysis Nature cell biology High 30858581
2019 MCU Cys-97 (N-terminal domain) is the target site of the cell-permeable MCU inhibitor Ru265. Site-directed mutagenesis of Cys-97 ablates Ru265 inhibitory activity. Site-directed mutagenesis, cell-based Ca2+ uptake assays, dose-response inhibition studies ACS central science High 30693334
2017 Tissue-specific stoichiometry of MICU1:MCU protein ratio controls the Ca2+ threshold and cooperativity of uniporter activation. Low MICU1:MCU ratio (heart, skeletal muscle) lowers the Ca2+ threshold for uptake; overexpression of MICU1 in heart increases MICU1:MCU ratio, causing liver-like mitochondrial Ca2+ uptake and cardiac contractile dysfunction. Quantitative protein ratio analysis, MICU1 pulldown proportional to overexpression, cardiac-specific MICU1 overexpression mouse model, Ca2+ uptake and contractile function measurements Cell reports High 28273446
2017 SLC25A23 interacts with MCU (CCDC109A) and MICU1, and increases IMiCa current. SLC25A23 EF-hand domain is required for this function; EF-hand mutants act as dominant negatives reducing mitochondrial Ca2+ uptake. Co-IP, IMiCa electrophysiology, RNAi knockdown, dominant-negative EF-hand mutant expression, mitochondrial Ca2+ imaging Molecular biology of the cell Medium 24430870
2017 Mitoxantrone is identified as a direct selective inhibitor of human MCU, validated in a reconstituted yeast system expressing human MCU and EMRE and in mammalian cell-based assays. High-throughput chemical screen using reconstituted yeast mitochondria with human MCU/EMRE and aequorin, mammalian cell Ca2+ uptake validation Molecular cell High 28820965
2015 Cytoplasmic Ca2+ elevation rearranges MICU1 multimers (EC50 ~4.4 µM), activating MCU/EMRE-dependent mitochondrial Ca2+ uptake. This rearrangement requires EF-hand motifs and is independent of matrix Ca2+ concentration, mitochondrial membrane potential, and MCU/EMRE expression levels. Live-cell FRET assay for MICU1 multimer rearrangement, EF-hand mutants, controlled cytosolic Ca2+ manipulation Scientific reports Medium 26489515
2017 MICU2 regulates the threshold and gain of MICU1-mediated inhibition and activation of MCU. MICU1 alone can mediate gatekeeping and highly cooperative MCU activation; MICU2 restricts spatial Ca2+ crosstalk between InsP3R and MCU channels by modulating MICU1's regulatory activity. Controlled cytoplasmic Ca2+ delivery with simultaneous recording of MCU activity, MICU1/MICU2 expression manipulation Cell reports Medium 29241542
2020 MCU channel activity is regulated by coupled Ca2+-sensing mechanisms on both sides of the inner mitochondrial membrane. Ca2+ permeating through the channel pore regulates Ca2+ affinities of inhibitory and activating sensors in the mitochondrial matrix. Ca2+ binding to an inhibitory sensor within the MCU amino terminus closes the channel even when MICU1/2 are Ca2+-bound. Disruption of MICU1/2 interaction with MCU complex disables matrix Ca2+ regulation. Electrophysiological recordings of MCU channel activity, controlled Ca2+ delivery on both sides of inner mitochondrial membrane, domain mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 32801213
2020 EMRE stoichiometry within the MCU complex controls channel gatekeeping. Most endogenous channels contain two EMRE per four MCU. Increasing EMRE:MCU ratio raises the Ca2+ threshold for channel activation. MCU-EMRE concatemers enforcing 1EMRE:4MCU restore Ca2+ uptake but not full gatekeeping; 4EMRE:4MCU enhances gatekeeping. Controlled EMRE:MCU expression ratios, MCU-EMRE concatemers, Ca2+ uptake and gatekeeping assays in cells lacking EMRE and MCU iScience Medium 32315830
2019 SPG7 directs the m-AAA protease complex to associate with MCU and controls MCU processing, which regulates higher-order MCU complex formation. Loss of SPG7 decreases functional uniporter complex formation, reducing mitochondrial Ca2+ concentration and conferring resistance to Ca2+-induced mPTP opening independent of cyclophilin D. SPG7 knockout, MCU complex assembly analysis, mitochondrial Ca2+ measurements, mPTP opening assays The Journal of biological chemistry Medium 31097542
2015 Ca2+ signals regulate MCU gene expression through CREB-mediated transcription. CREB directly binds the MCU promoter and stimulates its expression in response to cytoplasmic Ca2+ signals generated by IP3R, STIM1, and Orai1. Loss of these Ca2+ entry pathways reduces MCU abundance and mitochondrial Ca2+ uptake capacity. Chromatin immunoprecipitation (ChIP), promoter reporter assay, genetic deletion of IP3R/STIM1/Orai1 in DT40 B cells, MCU abundance measurements Science signaling High 25737585
2022 CaMKIIδB phosphorylates CREB, which binds the MCU promoter to upregulate Mcu gene transcription in cardiomyocytes. Isoproterenol-induced β-adrenergic stimulation upregulates MCU through the β-AR/CaMKIIδB/CREB pathway. Calcineurin-mediated dephosphorylation at Ser332 promotes nuclear translocation of CaMKIIδB to execute this transcriptional regulation. MCU KO and cardiac-specific MCU overexpression mouse models, adenoviral gene manipulation, CREB phosphorylation and promoter binding assays, intracellular Ca2+ handling measurements Circulation High 35167328
2013 MCU is mitochondrially localized and its expression is subject to activity-dependent transcriptional regulation in neurons. Synaptic activity transcriptionally represses Mcu via nuclear Ca2+ and CaM kinase-mediated induction of Npas4, reducing NMDA receptor-induced mitochondrial Ca2+ uptake and protecting against excitotoxic death. Exogenous MCU expression with mitochondrial localization imaging, MCU knockdown, NMDA stimulation, Ca2+ and cell death assays, Npas4-dependent transcriptional repression assay Nature communications High 23774321
2018 RIPK1 physically interacts with MCU to promote mitochondrial Ca2+ uptake and energy metabolism, driving colorectal cancer cell proliferation. The ubiquitination site RIPK1-K377 is critical for MCU interaction. Co-immunoprecipitation, RIPK1 overexpression and knockdown, mitochondrial Ca2+ measurement, proliferation assays, domain mutant analysis Cancer research Medium 29531160
2018 MCU interacts with Miro1 through MCU's N-terminal domain, which traverses the outer mitochondrial membrane. This MCU-Miro1 interaction is required for Miro1-directed mitochondrial movement in neurons. The N-terminus is dispensable for MCU mitochondrial targeting but critical for Miro1 interaction. Co-immunoprecipitation, domain deletion/mutation analysis, mitochondrial localization imaging, mitochondrial movement assays in neurons The Journal of neuroscience Medium 29686046
2019 MCU deletion in mouse liver (MCUΔhep) inhibits mitochondrial Ca2+ uptake, delays cytosolic Ca2+ clearance, reduces oxidative phosphorylation, and causes hepatic lipid accumulation. This is mediated by extramitochondrial Ca2+-dependent protein phosphatase-4 (PP4) activity that dephosphorylates and inactivates AMPK. PP4 knockdown or AMPK reconstitution reverses lipid accumulation; gain-of-function MCU decreases PP4 and reduces lipid accumulation. Liver-specific Mcu gene deletion (CRISPR/Cas9 in zebrafish, Cre-lox in mice), PP4 activity assay, AMPK phosphorylation analysis, lipid quantification, reconstitution experiments Cell reports High 30917323
2019 Loss of MCU prevents mitochondrial fusion during G1-S phase and blocks cell cycle progression and proliferation. MCU-null cells show baseline CaMKII activation, increased Drp1 Ser616 phosphorylation, mitochondrial fragmentation, and impaired respiration. Inhibition of cytosolic CaMKII or mitochondrial fission rescues these defects, revealing a regulatory circuit between MCU, cytosolic CaMKII, and Drp1-mediated fission/fusion. MCU genetic deletion, cell cycle analysis, CaMKII and Drp1 phosphorylation assays, mitochondrial fusion/fission imaging, MCU rescue experiments Science signaling High 31040260
2016 Crystal structure of CCDC90B (paralog of MCUR1) head domain reveals a conserved head-neck-stalk-anchor architecture. The head domain of MCUR1 directly interacts with MCU and is destabilized upon Ca2+ binding, providing structural details for MCU-MCUR1 complex formation. Crystal structure determination, protein binding assay, Ca2+ interaction analysis Structure Medium 30612859
2014 MCU interacts with VDAC1; MCU mediates VDAC1 overexpression-induced cell death in cerebellar granule neurons. MCU-VDAC1 complex regulates mitochondrial Ca2+ uptake and oxidative stress-induced apoptosis. Co-immunoprecipitation, MCU knockdown, mitochondrial Ca2+ imaging, cell death assays Protein & cell Low 25753332
2018 STAT3 (phospho-STAT3ser727) co-localizes and interacts with the N-terminal domain (NTD) of MCU in cardiomyocytes treated with moderate H2O2 postconditioning, inhibiting MCU opening and alleviating mitochondrial Ca2+ overload during ischemia-reperfusion. Co-localization/co-immunoprecipitation, STAT3 overexpression/shRNA, NTD domain-specific interaction mapping, mitochondrial Ca2+ measurements, cardiomyocyte I/R model Basic research in cardiology Medium 31463567
2021 HINT2 directly interacts with MCU and suppresses MCU complex activation, thereby reducing mitochondrial Ca2+ overload in cardiac microvascular endothelial cells. HINT2 overexpression inhibits the MCU complex-mitochondrial Ca2+ overload-mitochondrial fission-apoptosis pathway; re-activation of MCU by spermine abolishes HINT2 protection. Co-immunoprecipitation, HINT2 overexpression, mitochondrial Ca2+ measurement, MCU agonist (spermine) rescue experiment, in vivo I/R model Basic research in cardiology Medium 34914018
2017 MCU-dependent mitochondrial Ca2+ uptake promotes ROS production by downregulating NAD+/NADH ratio and inhibiting SIRT3 deacetylase activity, thereby inhibiting SOD2 activity. This leads to ROS-activated JNK pathway and MMP-2 activation promoting cancer cell migration and metastasis. MCU overexpression/knockdown, mitochondrial Ca2+ imaging, NAD+/NADH ratio measurement, SIRT3 activity assay, SOD2 activity assay, JNK phosphorylation, invasion/migration assays, xenograft model Oncogene Medium 28650465
2020 MCU-induced mitochondrial Ca2+ uptake inhibits phosphorylation of TFAM, enhancing its stability and promoting mitochondrial biogenesis, which increases mitochondrial ROS and activates NF-κB signaling to promote colorectal cancer cell growth. MCU overexpression/knockdown, TFAM phosphorylation assays, mitochondrial biogenesis markers, ROS measurement, NF-κB activation, xenograft model Signal transduction and targeted therapy Medium 32371956
2020 Inhibition of mitochondrial pyruvate transport or fatty acid flux triggers EGR1-mediated upregulation of MICU1 (not MCU core subunit), inhibiting MCU-mediated mitochondrial Ca2+ uptake. This reveals a TCA substrate-availability feedback circuit protecting cells from bioenergetic crisis and Ca2+ overload during nutrient stress. MPC isoform knockdown, dominant-negative MPC1R97W, MPC1 genetic ablation in hepatocytes and MEFs, MICU1 protein abundance assays, EGR1 transcription factor identification, mitochondrial Ca2+ measurements Science signaling Medium 32317369
2018 Parkin (PARK2) interacts with MICU1 (an MCU complex regulator) and promotes its proteasomal degradation via the UPS. Parkin's Ubl domain, but not its E3-ubiquitin ligase activity, is required for MICU1 degradation. Loss of Parkin function impairs mitochondrial Ca2+ handling. Co-immunoprecipitation, UPS inhibitor treatment, Parkin domain mutants, MICU1 stability assays, mitochondrial Ca2+ measurements Scientific reports Medium 30242232
2018 MICU1 confers protection from MCU-dependent manganese toxicity. Reconstitution of MCU and EMRE in yeast enhances manganese stress; co-expression of MICU1 prevents this. In human cells, MICU1 deletion sensitizes cells to manganese-dependent cell death by disinhibiting MCU-mediated manganese uptake, causing oxidative stress preventable by NAC. Synthetic biology reconstitution in yeast, MICU1 deletion in human cells, manganese stress assays, oxidative stress measurement Cell reports High 30403999
2019 Pyk2 directly phosphorylates MCU to enhance mitochondrial Ca2+ uptake in neurons. The Pyk2/MCU pathway is activated in rat cerebral ischemia, causing mitochondrial dysfunction and neuronal apoptosis. Pyk2 inhibitor (PF-431396) prevents MCU-dependent mitochondrial Ca2+ overload and cell death. Rat MCAO ischemia model, Pyk2 inhibitor treatment, mitochondrial Ca2+ measurement, mitochondrial dysfunction and apoptosis assays Neuroscience research Low 28916471
2023 MARS2 (mitochondrial methionyl-tRNA synthetase) interacts with MCU and stimulates mitochondrial Ca2+ influx. Methionine binding to MARS2 acts as a molecular switch regulating the MARS2-MCU interaction. Knockdown of MARS2 attenuates mitochondrial Ca2+ influx and induces downstream CaMKII/CREB signaling and metabolic rewiring. Co-immunoprecipitation, MARS2 knockdown, mitochondrial Ca2+ measurement, Ca2+-dependent signaling assays Redox biology Medium 36774778
2023 MCU activates mitochondrial respiration and net reduction of mitochondrial (but not cytosolic) redox state. MCU stimulation modulates redox-sensitive groups required for maintaining respiratory capacity in human myotubes and C. elegans. This redox modulation promotes mobility in worms. Mitochondria-targeted redox and calcium sensors, MCU genetic ablation models in human myotubes and C. elegans, direct pharmacological mitochondrial protein reduction Redox biology Medium 37302345
2023 Cd upregulates MCU expression through CREB phosphorylation at Ser133 binding to the MCU promoter (at TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions). Upregulated MCU intensively interacts with VDAC1, enhances VDAC1 dimerization and ubiquitination, resulting in excessive mitophagy and hepatotoxicity. CREB phosphorylation assay, MCU promoter ChIP/reporter analysis, Co-IP for MCU-VDAC1, VDAC1 ubiquitination assay, MCU siRNA/Ru360, heterozygous MCU KO mice Advanced science Medium 36642847
2014 ERp57 regulates the expression of MCU and modulates mitochondrial Ca2+ uptake. Silencing ERp57 downregulates MCU protein level and inhibits mitochondrial Ca2+ uptake; re-expression of MCU in ERp57-knockdown cells restores mitochondrial Ca2+ uptake. ERp57 siRNA knockdown, MCU expression measurement, mitochondrial Ca2+ uptake assay, MCU rescue experiment FEBS letters Low 24815697
2020 In beta cell-specific Mcu-null mice, glucose-stimulated mitochondrial Ca2+ accumulation, ATP production, and insulin secretion are strongly inhibited. MCU deletion increases cytosolic Ca2+ concentration and improves mitochondrial membrane depolarization. MCU is thus required for normal glucose-stimulated insulin secretion in vivo. Beta cell-specific Mcu KO (Ins1Cre), live fluorescence Ca2+ and ATP imaging, patch-clamp electrophysiology, in vivo glucose tolerance tests Diabetologia High 32350566
2021 In MCU-KO hearts, no alternative Ca2+ uptake mechanisms are detected, confirming MCU is the sole route for mitochondrial Ca2+ entry under the conditions tested. Optical mitochondrial Ca2+ measurement in intact perfused MCU-KO hearts, adrenergic stimulation Cell reports Medium 34686324
2024 In Duchenne muscular dystrophy mitochondria, an MCU-independent Ca2+ uptake mechanism exists that is sufficient to drive mitochondrial permeability transition pore activation and skeletal muscle necrosis. Myofiber-specific Mcu gene deletion was not protective and did not prevent mitochondrial Ca2+ overload in this disease model. Myofiber-specific Mcu gene deletion, Mcub gene deletion, mitochondrial Ca2+ measurement, muscle histopathology, muscle function tests Scientific reports Medium 38514795
2022 Cardiolipin (CL) is required for the abundance and stability of the MCU complex regulatory subunit MICU1, but not for MCU itself. In Barth syndrome (CL deficiency), reduced MICU1 perturbs the kinetics of MICU1-dependent mitochondrial Ca2+ uptake and impairs pyruvate dehydrogenase activation and mitochondrial bioenergetics. Multiple BTHS models (yeast, mouse myoblasts, patient cells/cardiac tissue), MICU1 stability assays, MCU/MICU1/MICU2/EMRE/MCUR1 abundance measurements, mitochondrial Ca2+ uptake kinetics, PDH activation assay Human molecular genetics Medium 34494107

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 1575 21685886
2012 MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell 575 23101630
2013 Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals. Nature communications 218 23774321
2017 Mitochondrial Ca2+ Uniporter Is a Mitochondrial Luminal Redox Sensor that Augments MCU Channel Activity. Molecular cell 201 28262504
2016 MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics. Cell reports 184 27184846
2015 The Ca(2+)-Dependent Release of the Mia40-Induced MICU1-MICU2 Dimer from MCU Regulates Mitochondrial Ca(2+) Uptake. Cell metabolism 169 26387864
2017 Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU. Cell reports 165 28273446
2017 MCU-dependent mitochondrial Ca2+ inhibits NAD+/SIRT3/SOD2 pathway to promote ROS production and metastasis of HCC cells. Oncogene 165 28650465
2016 The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria. Molecular cell 164 27642048
2013 MCU encodes the pore conducting mitochondrial calcium currents. eLife 157 23755363
2012 The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic β-cells. PloS one 151 22829870
2015 Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart. Proceedings of the National Academy of Sciences of the United States of America 148 26153425
2019 A Selective and Cell-Permeable Mitochondrial Calcium Uniporter (MCU) Inhibitor Preserves Mitochondrial Bioenergetics after Hypoxia/Reoxygenation Injury. ACS central science 144 30693334
2013 The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles. The Journal of biological chemistry 135 23400777
2020 MCU-induced mitochondrial calcium uptake promotes mitochondrial biogenesis and colorectal cancer growth. Signal transduction and targeted therapy 132 32371956
2014 SLC25A23 augments mitochondrial Ca²⁺ uptake, interacts with MCU, and induces oxidative stress-mediated cell death. Molecular biology of the cell 130 24430870
2019 AMPK-mediated activation of MCU stimulates mitochondrial Ca2+ entry to promote mitotic progression. Nature cell biology 125 30858581
2019 MCU Up-regulation contributes to myocardial ischemia-reperfusion Injury through calpain/OPA-1-mediated mitochondrial fusion/mitophagy Inhibition. Journal of cellular and molecular medicine 119 31502361
2017 Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening. Molecular cell 117 28820965
2012 Mitochondrial Ca2+ uptake 1 (MICU1) and mitochondrial ca2+ uniporter (MCU) contribute to metabolism-secretion coupling in clonal pancreatic β-cells. The Journal of biological chemistry 117 22904319
2015 Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU. Science signaling 114 25737585
2018 IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model. BMC nephrology 106 29907098
2018 MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca2+ Flux and Sensitivity to Ru360. Molecular cell 101 30454562
2018 Molecular regulation of MCU: Implications in physiology and disease. Cell calcium 100 29980025
2014 Unresolved questions from the analysis of mice lacking MCU expression. Biochemical and biophysical research communications 96 24792186
2022 Elevated MCU Expression by CaMKIIδB Limits Pathological Cardiac Remodeling. Circulation 91 35167328
2021 Protective effect of HINT2 on mitochondrial function via repressing MCU complex activation attenuates cardiac microvascular ischemia-reperfusion injury. Basic research in cardiology 91 34914018
2016 Efficient Synthesis of MCu (M = Pd, Pt, and Au) Aerogels with Accelerated Gelation Kinetics and their High Electrocatalytic Activity. Advanced materials (Deerfield Beach, Fla.) 91 27546519
2018 The role of the mitochondrial calcium uniporter (MCU) complex in cancer. Pflugers Archiv : European journal of physiology 85 29926229
2019 Blockade of MCU-Mediated Ca2+ Uptake Perturbs Lipid Metabolism via PP4-Dependent AMPK Dephosphorylation. Cell reports 80 30917323
2017 MICU2 Restricts Spatial Crosstalk between InsP3R and MCU Channels by Regulating Threshold and Gain of MICU1-Mediated Inhibition and Activation of MCU. Cell reports 79 29241542
2018 RIPK1 Binds MCU to Mediate Induction of Mitochondrial Ca2+ Uptake and Promotes Colorectal Oncogenesis. Cancer research 78 29531160
2015 Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death. Protein & cell 72 25753332
2019 Loss of MCU prevents mitochondrial fusion in G1-S phase and blocks cell cycle progression and proliferation. Science signaling 69 31040260
2021 MCU Overexpression Rescues Inotropy and Reverses Heart Failure by Reducing SR Ca2+ Leak. Circulation research 65 33522833
2020 Melatonin fine-tunes intracellular calcium signals and eliminates myocardial damage through the IP3R/MCU pathways in cardiorenal syndrome type 3. Biochemical pharmacology 65 32006470
2023 β-carotene targets IP3R/GRP75/VDAC1-MCU axis to renovate LPS-induced mitochondrial oxidative damage by regulating STIM1. Free radical biology & medicine 64 37270031
2017 HINT2 triggers mitochondrial Ca2+ influx by regulating the mitochondrial Ca2+ uniporter (MCU) complex and enhances gemcitabine apoptotic effect in pancreatic cancer. Cancer letters 64 28947137
2020 Mitochondrial pyruvate and fatty acid flux modulate MICU1-dependent control of MCU activity. Science signaling 63 32317369
2020 SERCA overexpression reduces reperfusion-mediated cardiac microvascular damage through inhibition of the calcium/MCU/mPTP/necroptosis signaling pathways. Redox biology 60 32738788
2019 The conserved aspartate ring of MCU mediates MICU1 binding and regulation in the mitochondrial calcium uniporter complex. eLife 60 30638448
2019 Cardioprotection of post-ischemic moderate ROS against ischemia/reperfusion via STAT3-induced the inhibition of MCU opening. Basic research in cardiology 58 31463567
2019 Restriction of mitochondrial calcium overload by mcu inactivation renders a neuroprotective effect in zebrafish models of Parkinson's disease. Biology open 58 31548178
2017 The MCU complex in cell death. Cell calcium 58 28867646
2023 MCU Upregulation Overactivates Mitophagy by Promoting VDAC1 Dimerization and Ubiquitination in the Hepatotoxicity of Cadmium. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 51 36642847
2018 MCU Interacts with Miro1 to Modulate Mitochondrial Functions in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 29686046
2020 Coupled transmembrane mechanisms control MCU-mediated mitochondrial Ca2+ uptake. Proceedings of the National Academy of Sciences of the United States of America 49 32801213
2018 The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation. American journal of physiology. Cell physiology 48 30020827
2015 Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.). Scientific reports 48 26489515
2023 The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases. Biomolecules 43 37759703
2018 Parkin-dependent regulation of the MCU complex component MICU1. Scientific reports 43 30242232
2020 The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice. Diabetologia 41 32350566
2020 The debate continues - What is the role of MCU and mitochondrial calcium uptake in the heart? Journal of molecular and cellular cardiology 40 32353353
2021 Monitoring mitochondrial calcium and metabolism in the beating MCU-KO heart. Cell reports 39 34686324
2020 Calcium influx through the mitochondrial calcium uniporter holocomplex, MCUcx. Journal of molecular and cellular cardiology 37 33147447
2020 MCU-dependent negative sorting of miR-4488 to extracellular vesicles enhances angiogenesis and promotes breast cancer metastatic colonization. Oncogene 36 33067576
2020 Redox Stability Controls the Cellular Uptake and Activity of Ruthenium-Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU). Angewandte Chemie (International ed. in English) 34 32039530
2021 MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous Ca2+ release in hypertrophic rat cardiomyocytes. American journal of physiology. Heart and circulatory physiology 32 34415186
2022 MCU controls melanoma progression through a redox-controlled phenotype switch. EMBO reports 31 36156348
2020 Mechanisms of EMRE-Dependent MCU Opening in the Mitochondrial Calcium Uniporter Complex. Cell reports 30 33296646
2018 MCU-knockdown attenuates high glucose-induced inflammation through regulating MAPKs/NF-κB pathways and ROS production in HepG2 cells. PloS one 30 29709004
2018 MICU1 Confers Protection from MCU-Dependent Manganese Toxicity. Cell reports 30 30403999
2013 Mitochondrial Ca(2+) uniporter (MCU)-dependent and MCU-independent Ca(2+) channels coexist in the inner mitochondrial membrane. Pflugers Archiv : European journal of physiology 30 24162235
2023 The mitochondrial Ca2+ channel MCU is critical for tumor growth by supporting cell cycle progression and proliferation. Frontiers in cell and developmental biology 29 37363724
2019 SPG7 targets the m-AAA protease complex to process MCU for uniporter assembly, Ca2+ influx, and regulation of mitochondrial permeability transition pore opening. The Journal of biological chemistry 29 31097542
2015 UCP2 modulates single-channel properties of a MCU-dependent Ca(2+) inward current in mitochondria. Pflugers Archiv : European journal of physiology 29 26275882
2024 MCU complex: Exploring emerging targets and mechanisms of mitochondrial physiology and pathology. Journal of advanced research 28 38417574
2016 Expression of mRNA Encoding Mcu and Other Mitochondrial Calcium Regulatory Genes Depends on Cell Type, Neuronal Subtype, and Ca2+ Signaling. PloS one 28 26828201
2021 MCU-Dependent mROS Generation Regulates Cell Metabolism and Cell Death Modulated by the AMPK/PGC-1α/SIRT3 Signaling Pathway. Frontiers in medicine 27 34307407
2020 Mitochondrial Calcium Uniporter (MCU) deficiency reveals an alternate path for Ca2+ uptake in photoreceptor mitochondria. Scientific reports 27 32994451
2022 MCU-dependent mitochondrial calcium uptake-induced mitophagy contributes to apelin-13-stimulated VSMCs proliferation. Vascular pharmacology 26 35306208
2017 The Pyk2/MCU pathway in the rat middle cerebral artery occlusion model of ischemic stroke. Neuroscience research 26 28916471
2022 MCU knockdown in hippocampal neurons improves memory performance of an Alzheimer's disease mouse model. Acta biochimica et biophysica Sinica 25 36239352
2022 MCU-complex-mediated mitochondrial calcium signaling is impaired in Barth syndrome. Human molecular genetics 24 34494107
2020 The mechanism of CaMK2α-MCU-mitochondrial oxidative stress in bupivacaine-induced neurotoxicity. Free radical biology & medicine 24 32275945
2013 Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons. Frontiers in cellular neuroscience 24 24058334
2023 Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders. Frontiers in neuroscience 23 37928737
2020 Variable Assembly of EMRE and MCU Creates Functional Channels with Distinct Gatekeeping Profiles. iScience 23 32315830
2020 Mitochondrial Ca2+ Dynamics in MCU Knockout C. elegans Worms. International journal of molecular sciences 22 33207633
2024 Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models. Cell reports 21 38236772
2024 Effects of hesperidin on mitochondrial function, mitochondria-associated endoplasmic reticulum membranes and IP3R-MCU calcium axis in the intestine of piglets exposed to deoxynivalenol. Food & function 20 38804659
2023 MARS2 drives metabolic switch of non-small-cell lung cancer cells via interaction with MCU. Redox biology 20 36774778
2023 miR-138-5p targets MCU to inhibit mitochondrial biogenesis and colorectal cancer growth. Journal of cellular and molecular medicine 20 37264759
2019 Characterization of MCU-Binding Proteins MCUR1 and CCDC90B - Representatives of a Protein Family Conserved in Prokaryotes and Eukaryotic Organelles. Structure (London, England : 1993) 20 30612859
2024 MCU-independent Ca2+ uptake mediates mitochondrial Ca2+ overload and necrotic cell death in a mouse model of Duchenne muscular dystrophy. Scientific reports 19 38514795
2022 Grpel2 alleviates myocardial ischemia/reperfusion injury by inhibiting MCU-mediated mitochondrial calcium overload. Biochemical and biophysical research communications 19 35447394
2022 Ruthenium red attenuates acute pancreatitis by inhibiting MCU and improving mitochondrial function. Biochemical and biophysical research communications 18 36283336
2014 ERp57 modulates mitochondrial calcium uptake through the MCU. FEBS letters 18 24815697
2025 Sigma-1 receptor activation attenuates DOX-induced cardiotoxicity by alleviating endoplasmic reticulum stress and mitochondrial calcium overload via PERK and IP3R-VDAC1-MCU signaling pathways. Biology direct 17 40001213
2020 Is MCU dispensable for normal heart function? Journal of molecular and cellular cardiology 17 32389793
2019 High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells. Oxidative medicine and cellular longevity 17 30911349
2023 Cadmium induced mouse spermatogonia apoptosis via mitochondrial calcium overload mediated by IP3R-MCU signal pathway. Toxicology 16 36731763
2020 Structure and Reconstitution of an MCU-EMRE Mitochondrial Ca2+ Uniporter Complex. Journal of molecular biology 16 32841658
2019 Slow Ca2+ Efflux by Ca2+/H+ Exchange in Cardiac Mitochondria Is Modulated by Ca2+ Re-uptake via MCU, Extra-Mitochondrial pH, and H+ Pumping by FOF1-ATPase. Frontiers in physiology 16 30804812
2023 The effect of regulating MCU expression on experimental ischemic brain injury. Experimental neurology 15 36702427
2023 Regulation of neuronal energy metabolism by calcium: Role of MCU and Aralar/malate-aspartate shuttle. Biochimica et biophysica acta. Molecular cell research 15 36997074
2021 miR-129-3p Targeting of MCU Protects Against Glucose Fluctuation-Mediated Neuronal Damage via a Mitochondrial-Dependent Intrinsic Apoptotic Pathway. Diabetes, metabolic syndrome and obesity : targets and therapy 15 33488104
2021 Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis. Frontiers in cell and developmental biology 15 34026753
2023 The mitochondrial calcium uniporter (MCU) activates mitochondrial respiration and enhances mobility by regulating mitochondrial redox state. Redox biology 14 37302345
2022 MCU Inhibitor Ruthenium Red Alleviates the Osteoclastogenesis and Ovariectomized Osteoporosis via Suppressing RANKL-Induced ROS Production and NFATc1 Activation through P38 MAPK Signaling Pathway. Oxidative medicine and cellular longevity 14 36148414

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