ArticleBiophysical journal2013
An integrated mitochondrial ROS production and scavenging model: implications for heart failure.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
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- Origins of Ultrasensitivity and Complex Signaling Dynamics of Cellular Hydrogen Peroxide and Peroxiredoxin.Antioxidants (Basel, Switzerland) · 2025Article
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- Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.The journal of cardiovascular aging · 2024Article
- Stachydrine Hydrochloride Regulates the NOX2-ROS-Signaling Axis in Pressure-Overload-Induced Heart Failure.International journal of molecular sciences · 2023Article
- Effects of ROS pathway inhibitors and NADH and FADHArchives of biochemistry and biophysics · 2023Article
- Kinetic Mathematical Modeling of Oxidative Phosphorylation in Cardiomyocyte Mitochondria.Cells · 2022Review
- SR-Mitochondria Crosstalk Shapes Ca Signalling to Impact Pathophenotype in Disease Models Marked by Dysregulated Intracellular Ca Release.Cardiovascular research · 2022Article
- Solving the Evidence Interpretability Crisis in Health Technology Assessment: A Role for Mechanistic Models?Frontiers in medical technology · 2022Article
- Profiling the chemical nature of anti-oxytotic/ferroptotic compounds with phenotypic screening.Free radical biology & medicine · 2021Article
- Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models.Antioxidants (Basel, Switzerland) · 2021Review
- Identifying Site-Specific Superoxide and Hydrogen Peroxide Production Rates From the Mitochondrial Electron Transport System Using a Computational Strategy.Function (Oxford, England) · 2021Article
- Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release.Scientific reports · 2020Article
- Kinetic modeling of H2O2 dynamics in the mitochondria of HeLa cells.PLoS computational biology · 2020Article
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Systems Biology Approaches Toward Understanding Primary Mitochondrial Diseases.Frontiers in genetics · 2019Review
- Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons.Cardiovascular research · 2018Article
- Vitamin K2 Prevents Lymphoma in Drosophila.Scientific reports · 2017Article
- Modeling oxygen requirements in ischemic cardiomyocytes.The Journal of biological chemistry · 2017Article
- Mitochondrial contribution to lipofuscin formation.Redox biology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
It has been observed experimentally that cells from failing hearts exhibit elevated levels of reactive oxygen species (ROS) upon increases in energetic workload. One proposed mechanism for this behavior is mitochondrial Ca(2+) mismanagement that leads to depletion of ROS scavengers. Here, we present a computational model to test this hypothesis. Previously published models of ROS production and scavenging were combined and reparameterized to describe ROS regulation in the cellular environment. Extramitochondrial Ca(2+) pulses were applied to simulate frequency-dependent changes in cytosolic Ca(2+). Model results show that decreased mitochondrial Ca(2+)uptake due to mitochondrial Ca(2+) uniporter inhibition (simulating Ru360) or elevated cytosolic Na(+), as in heart failure, leads to a decreased supply of NADH and NADPH upon increasing cellular workload. Oxidation of NADPH leads to oxidation of glutathione (GSH) and increased mitochondrial ROS levels, validating the Ca(2+) mismanagement hypothesis. The model goes on to predict that the ratio of steady-state [H2O2]m during 3Hz pacing to [H2O2]m at rest is highly sensitive to the size of the GSH pool. The largest relative increase in [H2O2]m in response to pacing is shown to occur when the total GSH and GSSG is close to 1 mM, whereas pool sizes below 0.9 mM result in high resting H2O2 levels, a quantitative prediction only possible with a computational model.
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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.