ArticleNature communications2015
The mitochondrial uniporter controls fight or flight heart rate increases.
Article in Nature communications, 2015. 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 112 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Knowledge mapping of mitochondrial calcium uniporter from 2011 to 2022: A bibliometric analysis.Frontiers in physiology · 2023Pooled it
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Increased Intermembrane Space [CaCirculation research · 2025Article
- Impaired cardiac non-neuronal acetylcholine synthesis triggers mitochondrial dysfunction with the loss of nicotinic receptor-mediated calcium handling, causing the failing heart.Clinical science (London, England : 1979) · 2025Article
- Calmodulin enhancement of mitochondrial calcium uniporter function in isolated mitochondria.Cell calcium · 2025Article
- A simulation study on the role of mitochondria-sarcoplasmic reticulum CaThe Journal of physiology · 2025Article
- NR3C1/GLMN-Mediated FKBP12.6 Ubiquitination Disrupts Calcium Homeostasis and Impairs Mitochondrial Quality Control in Stress-Induced Myocardial Damage.International journal of molecular sciences · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Enhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HCN4 channels sense temperature and determine heart rate responses to heat.Nature communications · 2025Article
- Metabolic-stress-induced mitochondrial calcium dysregulation: a central hub in diabetic cardiomyopathy pathogenesis and treatment.Frontiers in endocrinology · 2025Review
- A Mitochondrial Basis for Heart Failure Progression.Cardiovascular drugs and therapy · 2024Review
- Neuronal Mitochondrial Calcium Uniporter (MCU) Deficiency Is Neuroprotective in Hyperexcitability by Modulation of Metabolic Pathways and ROS Balance.Molecular neurobiology · 2024Article
- Sex differences in cardiac mitochondrial respiration and reactive oxygen species production may predisposeJournal of molecular and cellular cardiology plus · 2024Article
- MICU1 and MICU2 control mitochondrial calcium signaling in the mammalian heart.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Calcium signaling from sarcoplasmic reticulum and mitochondria contact sites in acute myocardial infarction.Journal of translational medicine · 2024Review
- Electro-metabolic coupling in multi-chambered vascularized human cardiac organoids.Nature biomedical engineering · 2023Article
- The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases.Biomolecules · 2023Review
- Integrated Comparative Transcriptome and circRNA-lncRNA-miRNA-mRNA ceRNA Regulatory Network Analyses Identify Molecular Mechanisms Associated with Intramuscular Fat Content in Beef Cattle.Animals : an open access journal from MDPI · 2023Article
- Mitochondrial calcium and reactive oxygen species in cardiovascular disease.Cardiovascular research · 2023Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.
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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.