ArticleScientific reports2020
The iron chelator Deferasirox causes severe mitochondrial swelling without depolarization due to a specific effect on inner membrane permeability.
Article in Scientific reports, 2020. 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, 37 citations in OpenAlex.
- Impact of renal iron overload on sickle cell nephropathy in a humanized mouse model.American journal of physiology. Renal physiology · 2026Article
- When our treatment is complicated: an overview of drug-induced acid-base disorders: part 1-acidosis.Pediatric nephrology (Berlin, Germany) · 2026Review
- Nanotechnology-Driven Precision Modulation of Transplant Immunity: From Mechanistic Insights to Clinical Tolerance.International journal of nanomedicine · 2026Review
- Ferroptosis: a promising therapeutic target for periodontitis.Frontiers in immunology · 2026Review
- Pharmacovigilance assessment of drug-induced aplastic anemia: analysis of the FDA adverse event reporting system.International journal of clinical pharmacy · 2025Article
- Elucidating the High Affinity Copper(II) Complexation by the Iron Chelator Deferasirox Provides Therapeutic and Toxicity Insight.ChemMedChem · 2025Article
- Intranasal delivery of iron chelators and management of central nervous system disease.Frontiers in pharmacology · 2025Review
- Deferasirox, an iron chelator, impacts myeloid differentiation by modulating NF-kB activity via mitochondrial ROS.British journal of haematology · 2024Article
- Deferasirox's Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma.Biomedicines · 2024Article
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- Case report: Acute liver failure during deferasirox therapy and the potential role of pharmacogenetics.Frontiers in pharmacology · 2024Article
- Neuroinflammation and iron metabolism after intracerebral hemorrhage: a glial cell perspective.Frontiers in neurology · 2024Review
- Deferasirox and Ciprofloxacin: Potential Ternary Complex Formation With Ferric Iron, Pharmacodynamic, and Pharmacokinetic Interactions.TheScientificWorldJournal · 2024Article
- Chelators as Antineuroblastomas Agents.Physiological research · 2023Article
- Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells.Current issues in molecular biology · 2023Article
- Metabolic mechanisms of acute proximal tubular injury.Pflugers Archiv : European journal of physiology · 2022Review
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- Drug toxicity in the proximal tubule: new models, methods and mechanisms.Pediatric nephrology (Berlin, Germany) · 2022Review
- Therapeutic potential of induced iron depletion using iron chelators in Covid-19.Saudi journal of biological sciences · 2022Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The iron chelator Deferasirox (DFX) causes severe toxicity in patients for reasons that were previously unexplained. Here, using the kidney as a clinically relevant in vivo model for toxicity together with a broad range of experimental techniques, including live cell imaging and in vitro biophysical models, we show that DFX causes partial uncoupling and dramatic swelling of mitochondria, but without depolarization or opening of the mitochondrial permeability transition pore. This effect is explained by an increase in inner mitochondrial membrane (IMM) permeability to protons, but not small molecules. The movement of water into mitochondria is prevented by altering intracellular osmotic gradients. Other clinically used iron chelators do not produce mitochondrial swelling. Thus, DFX causes organ toxicity due to an off-target effect on the IMM, which has major adverse consequences for mitochondrial volume regulation.
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