ArticleScience signaling2015
Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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
76 citing papers in PubMed, 122 citations in OpenAlex.
- The Effects of Disrupting CaMarine biotechnology (New York, N.Y.) · 2026Article
- Dysregulated calcium signaling underlies hyposalivation and microbial dysbiosis in Down syndrome.Cell reports · 2026Article
- Grape Seed Extract as an Adjuvant Therapy for Huntington Disease; A Narrative Review of Biological Plausibility and Potential Clinical Outcomes.Molecules (Basel, Switzerland) · 2026Review
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- STIM1-containing contact sites promote direct calcium flux from the endoplasmic reticulum to mitochondria.The EMBO journal · 2026Article
- Transcellular mitochondrial transfer from hypermetabolic astrocytes to neurons during cocaine and HIV-1 exposure.Cell communication and signaling : CCS · 2025Article
- Ferritinophagy Loss Drives Mitochondrial Iron Import and Colorectal Tumorigenesis.Research square · 2025Article
- Mitochondrial CaJournal of cellular physiology · 2025Review
- Mitochondrial Calcium Uniporter Regulates Metabolic Remodeling and Smooth Muscle Cell Proliferation in Type 2 Diabetes.Journal of the American Heart Association · 2025Article
- Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The ROS Mediates MCUb in Mitochondria-Regulated Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.Biological trace element research · 2025Article
- Mrs2-mediated mitochondrial magnesium uptake is essential for the regulation of MCU-mediated mitochondrial CaMitochondrion · 2024Article
- α-Hederin induces paraptosis by targeting GPCRs to activate CaCancer medicine · 2024Article
- Mitochondrial CaJACC. Basic to translational science · 2024Article
- Chronic exercise improves hepatic acylcarnitine handling.iScience · 2024Article
- Effects of hindlimb unloading on the mevalonate and mechanistic target of rapamycin complex 1 signaling pathways in a fast-twitch muscle in rats.Physiological reports · 2024Article
- APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway inInternational journal of molecular sciences · 2023Article
- HIV-1 gp120 protein promotes HAND through the calcineurin pathway activation.Mitochondrion · 2023Article
- Article
- Mitotic events depend on regulation of PLK-1 levels by the mitochondrial protein SPD-3.bioRxiv : the preprint server for biology · 2023Article
16 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
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Cytosolic Ca2+ signals, generated through the coordinated translocation of Ca2+ across the plasma membrane (PM) and endoplasmic reticulum (ER) membrane, mediate diverse cellular responses. Mitochondrial Ca2+ is important for mitochondrial function, and when cytosolic Ca2+ concentration becomes too high, mitochondria function as cellular Ca2+ sinks. By measuring mitochondrial Ca2+ currents, we found that mitochondrial Ca2+ uptake was reduced in chicken DT40 B lymphocytes lacking either the ER-localized inositol trisphosphate receptor (IP3R), which releases Ca2+ from the ER, or Orai1 or STIM1, components of the PM-localized Ca2+ -permeable channel complex that mediates store-operated calcium entry (SOCE) in response to depletion of ER Ca2+ stores. The abundance of MCU, the pore-forming subunit of the mitochondrial Ca2+ uniporter, was reduced in cells deficient in IP3R, STIM1, or Orai1. Chromatin immunoprecipitation and promoter reporter analyses revealed that the Ca2+ -regulated transcription factor CREB (cyclic adenosine monophosphate response element-binding protein) directly bound the MCU promoter and stimulated expression. Lymphocytes deficient in IP3R, STIM1, or Orai1 exhibited altered mitochondrial metabolism, indicating that Ca2+ released from the ER and SOCE-mediated signals modulates mitochondrial function. Thus, our results showed that a transcriptional regulatory circuit involving Ca2+ -dependent activation of CREB controls the Ca2+ uptake capability of mitochondria and hence regulates mitochondrial metabolism.
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.