ArticleCommunications biology2021
Aberrant activity of mitochondrial NCLX is linked to impaired synaptic transmission and is associated with mental retardation.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Asymmetric distribution of mitochondrial CaExperimental & molecular medicine · 2026Article
- Molecular mechanisms of mitochondrial CaNature communications · 2026Article
- Mitochondrial regulation of brain development: evidence from zebrafish models.Fish physiology and biochemistry · 2026Review
- Mitochondrial dysfunction in neonatal brain injury: from molecular mechanisms to therapeutic interventions.Journal of translational medicine · 2026Review
- Early Reduction in Mitochondrial Membrane Potential in Synaptic Mitochondria Contribute to Synaptic Pathology in the EAE Mouse Model of Multiple Sclerosis.International journal of molecular sciences · 2026Article
- Role of mitochondria in neuronal function and survival in the enteric and central nervous systems.Cellular and molecular life sciences : CMLS · 2026Review
- Molecular mechanisms of mitochondrial CabioRxiv : the preprint server for biology · 2026Article
- Mitochondrial CaNature metabolism · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- Tmbim5 and Slc8b1 cooperate in tissue-specific mitochondrial calcium regulation in zebrafish.Communications biology · 2026Article
- Role of Mitochondrial Calcium Dysregulation in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2025Review
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Article
- TMEM65 functions as the mitochondrial NaNature cell biology · 2025Article
- Mitochondrial dysfunction mediated by ER-calcium dysregulation in neurons derived from Alzheimer's disease patients.Acta neuropathologica communications · 2025Article
- Temporal Changes in Mitochondria-Centric Excitotoxic Responses Following Severe Penetrating Traumatic Brain Injury.Biomedicines · 2025Article
- TMEM65 regulates and is required for NCLX-dependent mitochondrial calcium efflux.Nature metabolism · 2025Article
- Article
- Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.Translational psychiatry · 2024Article
- The mitochondria as a potential therapeutic target in cerebral I/R injury.Frontiers in neuroscience · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium dynamics control synaptic transmission. Calcium triggers synaptic vesicle fusion, determines release probability, modulates vesicle recycling, participates in long-term plasticity and regulates cellular metabolism. Mitochondria, the main source of cellular energy, serve as calcium signaling hubs. Mitochondrial calcium transients are primarily determined by the balance between calcium influx, mediated by the mitochondrial calcium uniporter (MCU), and calcium efflux through the sodium/lithium/calcium exchanger (NCLX). We identified a human recessive missense SLC8B1 variant that impairs NCLX activity and is associated with severe mental retardation. On this basis, we examined the effect of deleting NCLX in mice on mitochondrial and synaptic calcium homeostasis, synaptic activity, and plasticity. Neuronal mitochondria exhibited basal calcium overload, membrane depolarization, and a reduction in the amplitude and rate of calcium influx and efflux. We observed smaller cytoplasmic calcium transients in the presynaptic terminals of NCLX-KO neurons, leading to a lower probability of release and weaker transmission. In agreement, synaptic facilitation in NCLX-KO hippocampal slices was enhanced. Importantly, deletion of NCLX abolished long term potentiation of Schaffer collateral synapses. Our results show that NCLX controls presynaptic calcium transients that are crucial for defining synaptic strength as well as short- and long-term plasticity, key elements of learning and memory processes.
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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.