ArticleThe Journal of biological chemistry2007
Sequential opening of mitochondrial ion channels as a function of glutathione redox thiol status.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 196 citations in OpenAlex.
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Decreased ability to manage increases in reactive oxygen species may underlie susceptibility to arrhythmias in mice lackingAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Sex differences in cardiac mitochondrial respiration and reactive oxygen species production may predisposeJournal of molecular and cellular cardiology plus · 2024Article
- Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction.Cardiovascular diabetology · 2024Review
- Role of Mitochondrial ROS for Calcium Alternans in Atrial Myocytes.Biomolecules · 2024Article
- Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities.Journal of medicinal chemistry · 2024Review
- Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.Redox biology · 2023Review
- The cyclic lipopeptide micafungin induces rupture of isolated mitochondria by reprograming the mitochondrial inner membrane anion channel.Mitochondrion · 2023Article
- Post-translational modifications and protein quality control of mitochondrial channels and transporters.Frontiers in cell and developmental biology · 2023Review
- A new triphenylphosphonium-conjugated amphipathic cationic peptide with improved cell-penetrating and ROS-targeting properties.Current research in pharmacology and drug discovery · 2023Article
- S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Characterization of oxidation of glutathione by cytochrome c.Journal of bioenergetics and biomembranes · 2022Article
- Anti-aging Effects of Antioxidant Rare-Earth Orthovanadate Nanoparticles in Wistar Rats.Biological trace element research · 2021Article
- Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver.Journal of molecular cell biology · 2021Article
- Cellular Redox State Acts as Switch to Determine the Direction of NNT-Catalyzed Reaction in Cystic Fibrosis Cells.International journal of molecular sciences · 2021Article
- Hydrogen peroxide diffusion and scavenging shapes mitochondrial network instability and failure by sensitizing ROS-induced ROS release.Scientific reports · 2020Article
- Promising Polyphenols in Parkinson's Disease Therapeutics.Neurochemical research · 2020Review
- A multifunctional nanoprobe for targeting tumors and mitochondria with singlet oxygen generation and monitoring mitochondrion pH changes in cancer cells by ratiometric fluorescence imaging.Chemical science · 2020Article
- Diabetes Increases the Vulnerability of the Cardiac Mitochondrial Network to Criticality.Frontiers in physiology · 2020Article
- Pathophysiology of Calcium Mediated Ventricular Arrhythmias and Novel Therapeutic Options with Focus on Gene Therapy.International journal of molecular sciences · 2019Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial membrane potential (DeltaPsi(m)) depolarization contributes to cell death and electrical and contractile dysfunction in the post-ischemic heart. An imbalance between mitochondrial reactive oxygen species production and scavenging was previously implicated in the activation of an inner membrane anion channel (IMAC), distinct from the permeability transition pore (PTP), as the first response to metabolic stress in cardiomyocytes. The glutathione redox couple, GSH/GSSG, oscillated in parallel with DeltaPsi(m) and the NADH/NAD(+) redox state. Here we show that depletion of reduced glutathione is an alternative trigger of synchronized mitochondrial oscillation in cardiomyocytes and that intermediate GSH/GSSG ratios cause reversible DeltaPsi(m) depolarization, although irreversible PTP activation is induced by extensive thiol oxidation. Mitochondrial dysfunction in response to diamide occurred in stages, progressing from oscillations in DeltaPsi(m) to sustained depolarization, in association with depletion of GSH. Mitochondrial oscillations were abrogated by 4'-chlorodiazepam, an IMAC inhibitor, whereas cyclosporin A was ineffective. In saponin-permeabilized cardiomyocytes, the thiol redox status was systematically clamped at GSH/GSSG ratios ranging from 300:1 to 20:1. At ratios of 150:1-100:1, DeltaPsi(m) depolarized reversibly, and a matrix-localized fluorescent marker was retained; however, decreasing the GSH/GSSG to 50:1 irreversibly depolarized DeltaPsi(m) and induced maximal rates of reactive oxygen species production, NAD(P)H oxidation, and loss of matrix constituents. Mitochondrial GSH sensitivity was altered by inhibiting either GSH uptake, the NADPH-dependent glutathione reductase, or the NADH/NADPH transhydrogenase, indicating that matrix GSH regeneration or replenishment was crucial. The results indicate that GSH/GSSG redox status governs the sequential opening of mitochondrial ion channels (IMAC before PTP) triggered by thiol oxidation in cardiomyocytes.
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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.