ArticleNature communications2013
Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- Mitochondrial Proteomes in Neural Cells: A Systematic Review.Biomolecules · 2023Pooled it
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- Asymmetric distribution of mitochondrial CaExperimental & molecular medicine · 2026Article
- Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.The EMBO journal · 2026Article
- Mitochondrial Calcium Uniporter protects hippocampal CA2 neurons from NMDA-induced excitotoxic injury.Molecular medicine (Cambridge, Mass.) · 2026Article
- A paradoxical relationship between mitochondrial calcium regulation and retinal ganglion cell degeneration after axon damage.bioRxiv : the preprint server for biology · 2026Article
- Review
- Elevating levels of neuronal MCU in the hippocampus enhances mitochondrial calcium uptake and respiratory efficiency proportional to demand.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial CaNature metabolism · 2026Article
- Fuelling the brain with calcium.Nature metabolism · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- Mitochondrial unfolded protein response as a central stress-integration hub: mechanisms and implications in disease contexts.Burns & trauma · 2026Review
- Neurobiological and emotional impact of occupational stress in frontline police officers: a neuroimaging and neurochemical study.European journal of psychotraumatology · 2025Article
- Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.Neurochemical research · 2025Review
- Multi-Omic Analysis of Glutamate Excitotoxicity in Primary Neuronal Cultures.Journal of neurochemistry · 2025Article
- HDAC4 Inhibits NMDA Receptor-mediated Stimulation of Neurogranin Expression.Molecular neurobiology · 2025Article
- Article
- MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity.Scientific reports · 2025Article
- Article
101 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 1 institution in 1 country.
Funding
Abstract
The recent identification of the mitochondrial Ca(2+) uniporter gene (Mcu/Ccdc109a) has enabled us to address its role, and that of mitochondrial Ca(2+) uptake, in neuronal excitotoxicity. Here we show that exogenously expressed Mcu is mitochondrially localized and increases mitochondrial Ca(2+) levels following NMDA receptor activation, leading to increased mitochondrial membrane depolarization and excitotoxic cell death. Knockdown of endogenous Mcu expression reduces NMDA-induced increases in mitochondrial Ca(2+), resulting in lower levels of mitochondrial depolarization and resistance to excitotoxicity. Mcu is subject to dynamic regulation as part of an activity-dependent adaptive mechanism that limits mitochondrial Ca(2+) overload when cytoplasmic Ca(2+) levels are high. Specifically, synaptic activity transcriptionally represses Mcu, via a mechanism involving the nuclear Ca(2+) and CaM kinase-mediated induction of Npas4, resulting in the inhibition of NMDA receptor-induced mitochondrial Ca(2+) uptake and preventing excitotoxic death. This establishes Mcu and the pathways regulating its expression as important determinants of excitotoxicity, which may represent therapeutic targets for excitotoxic disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.