ArticleAmerican journal of physiology. Heart and circulatory physiology2015
Mitochondria-derived ROS bursts disturb Ca²⁺ cycling and induce abnormal automaticity in guinea pig cardiomyocytes: a theoretical study.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 54 citations in OpenAlex.
- Mitoquinone Prevents Cardiac Dysfunction by Normalizing Mitochondrial ROS and Calcium Handling in Acute Myocardial Infarction.Acta physiologica (Oxford, England) · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- The Sirt3-CD38 axis induces mitochondrial dysfunction in hypertrophied heart by regulating mitochondrial calcium overload.European journal of medical research · 2025Article
- Clumpy Novel Mitochondrial Signatures in Irradiated Human Diabetic Buccal Cells: A Case Control Study.Medeniyet medical journal · 2025Article
- TAB2 deficiency induces dilated cardiomyopathy by promoting mitochondrial calcium overload in human iPSC-derived cardiomyocytes.Molecular medicine (Cambridge, Mass.) · 2025Article
- PITX2 deficiency leads to atrial mitochondrial dysfunction.Cardiovascular research · 2024Article
- Guidelines for mechanistic modeling and analysis in cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2024Review
- Article
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Status of Mitochondrial Oxidative Phosphorylation during the Development of Heart Failure.Antioxidants (Basel, Switzerland) · 2023Review
- Mitochondrial Calcium Overload Plays a Causal Role in Oxidative Stress in the Failing Heart.Biomolecules · 2023Review
- Review
- Kinetic Mathematical Modeling of Oxidative Phosphorylation in Cardiomyocyte Mitochondria.Cells · 2022Review
- Cardiomyocyte NaBasic research in cardiology · 2021Article
- Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits.Oxidative medicine and cellular longevity · 2021Review
- Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases.Frontiers in cell and developmental biology · 2021Review
- Mitochondrial Dysfunction Contributes to Aging-Related Atrial Fibrillation.Oxidative medicine and cellular longevity · 2021Article
- Mitochondrial depolarization promotes calcium alternans: Mechanistic insights from a ventricular myocyte model.PLoS computational biology · 2021Article
- Unraveling the Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy: Obesity-Related Cardiac Defects as a Major Disease Modifier.Journal of the American Heart Association · 2020Review
- The debate continues - What is the role of MCU and mitochondrial calcium uptake in the heart?Journal of molecular and cellular cardiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondria are in close proximity to the redox-sensitive sarcoplasmic reticulum (SR) Ca(2+) release [ryanodine receptors (RyRs)] and uptake [Ca(2+)-ATPase (SERCA)] channels. Thus mitochondria-derived reactive oxygen species (mdROS) could play a crucial role in modulating Ca(2+) cycling in the cardiomyocytes. However, whether mdROS-mediated Ca(2+) dysregulation translates to abnormal electrical activities under pathological conditions, and if yes what are the underlying ionic mechanisms, have not been fully elucidated. We hypothesize that pathological mdROS induce Ca(2+) elevation by modulating SR Ca(2+) handling, which activates other Ca(2+) channels and further exacerbates Ca(2+) dysregulation, leading to abnormal action potential (AP). We also propose that the morphologies of elicited AP abnormality rely on the time of mdROS induction, interaction between mitochondria and SR, and intensity of mitochondrial oxidative stress. To test the hypotheses, we developed a multiscale guinea pig cardiomyocyte model that incorporates excitation-contraction coupling, local Ca(2+) control, mitochondrial energetics, and ROS-induced ROS release. This model, for the first time, includes mitochondria-SR microdomain and modulations of mdROS on RyR and SERCA activities. Simulations show that mdROS bursts increase cytosolic Ca(2+) by stimulating RyRs and inhibiting SERCA, which activates the Na(+)/Ca(2+) exchanger, Ca(2+)-sensitive nonspecific cationic channels, and Ca(2+)-induced Ca(2+) release, eliciting abnormal AP. The morphologies of AP abnormality are largely influenced by the time interval among mdROS burst induction and AP firing, dosage and diffusion of mdROS, and SR-mitochondria distance. This study defines the role of mdROS in Ca(2+) overload-mediated cardiac arrhythmogenesis and underscores the importance of considering mitochondrial targets in designing new antiarrhythmic therapies.
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.