ArticleBiochimica et biophysica acta
Redox-optimized ROS balance: a unifying hypothesis.
Article in Biochimica et biophysica acta. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 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.
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Who cites it
227 citing papers in PubMed, 1 synthesis or guideline pooled it, 370 citations in OpenAlex.
- Reprogramming heart failure: physiological orchestration and mechanistic decoding of exercise benefits.BMC cardiovascular disorders · 2025Pooled it
- Exercise-Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells.Oxidative medicine and cellular longevity · 2018Trial
- Mitochondrial heterogeneity across cardiac cell types in heart failure with preserved ejection fraction.Redox biology · 2026Review
- Resistance to atrial fibrillation domestication and mitochondrial dysfunction in sheep: a potential key role of the TCA cycle and mitochondrial redox state.Redox biology · 2026Article
- Mitochondrial superoxide-induced mitohormesis is mediated by citrate and cardioprotective.Science advances · 2026Article
- Hyperglycaemia-induced reactive oxygen species production in cardiac ventricular myocytes differs among mammals.The Journal of physiology · 2026Article
- PTGS2-Based Network Pharmacology and Molecular Modeling Investigation of the Antioxidant Potential of EthanolicLife (Basel, Switzerland) · 2026Article
- Plant-derived mitochondria mitigate aging-related neurodegeneration by reprogramming microglial mitochondrial energy metabolism.Translational neurodegeneration · 2026Article
- Mechanism of miR-140-3p reducing anesthesia induced neurotoxicity by downregulating BACE1 expression.Journal of neurovirology · 2026Article
- Malic enzyme-based system for transhydrogenation between nicotinamide cofactors.Synthetic and systems biotechnology · 2026Article
- Distinct profiles of mitochondrial bioenergetics and redox balance in left atrial and ventricular myocardium in the healthy rat heart.Experimental physiology · 2026Article
- Targeted Reduction of Excessive Mitochondrial Superoxide by Mitoquinone Rescues Cognitive Impairment Without Affecting Spontaneous Recurrent Seizures in a Mouse Model of Temporal Lobe Epilepsy.Antioxidants (Basel, Switzerland) · 2026Article
- Exploring the therapeutic potential of disulfiram in endometriosis: mechanisms targeting inflammation, oxidative stress, pyroptosis, and angiogenesis.Archives of gynecology and obstetrics · 2026Review
- Genotypic resilience and fruit quality responses of tomato (Frontiers in plant science · 2026Article
- Review
- Mechano-energetic uncoupling in heart failure.Nature reviews. Cardiology · 2025Review
- The Importance of Multifaceted Approach for Accurate and Comprehensive Evaluation of Oxidative Stress Status in Biological Systems.Antioxidants (Basel, Switzerland) · 2025Review
- Oxidative Stress and Neurotoxicity Biomarkers in Fish Toxicology.Antioxidants (Basel, Switzerland) · 2025Review
- Management of ROS and Regulatory Cell Death in Myocardial Ischemia-Reperfusion Injury.Molecular biotechnology · 2025Review
- The Dual Role of Oxidative Stress in Atherosclerosis and Coronary Artery Disease: Pathological Mechanisms and Diagnostic Potential.Antioxidants (Basel, Switzerland) · 2025Review
167 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
3 authors at 1 institution in 1 country.
Funding
Abstract
While it is generally accepted that mitochondrial reactive oxygen species (ROS) balance depends on the both rate of single electron reduction of O2 to superoxide (O2.-) by the electron transport chain and the rate of scavenging by intracellular antioxidant pathways, considerable controversy exists regarding the conditions leading to oxidative stress in intact cells versus isolated mitochondria. Here, we postulate that mitochondria have been evolutionarily optimized to maximize energy output while keeping ROS overflow to a minimum by operating in an intermediate redox state. We show that at the extremes of reduction or oxidation of the redox couples involved in electron transport (NADH/NAD+) or ROS scavenging (NADPH/NADP+, GSH/GSSG), respectively, ROS balance is lost. This results in a net overflow of ROS that increases as one moves farther away from the optimal redox potential. At more reduced mitochondrial redox potentials, ROS production exceeds scavenging, while under more oxidizing conditions (e.g., at higher workloads) antioxidant defenses can be compromised and eventually overwhelmed. Experimental support for this hypothesis is provided in both cardiomyocytes and in isolated mitochondria from guinea pig hearts. The model reconciles, within a single framework, observations that isolated mitochondria tend to display increased oxidative stress at high reduction potentials (and high mitochondrial membrane potential, Psim), whereas intact cardiac cells can display oxidative stress either when mitochondria become more uncoupled (i.e., low Psim) or when mitochondria are maximally reduced (as in ischemia or hypoxia). The continuum described by the model has the potential to account for many disparate experimental observations and also provides a rationale for graded physiological ROS signaling at redox potentials near the minimum.
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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.