ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Deubiquitinase OTUD5 as a Novel Protector against 4-HNE-Triggered Ferroptosis in Myocardial Ischemia/Reperfusion Injury.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 99 citations in OpenAlex.
- Article
- Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice.Redox report : communications in free radical research · 2026Article
- Cell death in ischemia-reperfusion injury: beyond a single-cell-death perspective.Biomarker research · 2026Review
- Reduced ALDH2 Activity and Cardiovascular Carbonyl Stress: From Reactive Aldehyde Networks to Coronary Microvascular Obstruction.Cardiovascular toxicology · 2026Review
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- ABHD11-Mediated mtDNA Transcription Restored Mitochondrial Function to Attenuate Cardiomyocyte Ferroptosis After Myocardial Infarction.Circulation · 2026Article
- Targeting ALDH2 with Alda-1 to reverse cisplatin resistance in lung adenocarcinoma.Cancer chemotherapy and pharmacology · 2026Article
- Ferroptotic propagation: from single-cell execution to tissue-scale death programs.Cell research · 2026Review
- 4-Hydroxytamoxifen induces a noncanonical ferroptosis in lung adenocarcinoma by targeting AKR1B10.Clinical and translational medicine · 2026Article
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- Plasma exosomal miR-339-3p promotes myocardial remodeling in chronic heart failure by regulating USP25-mediated DDX58 deubiquitination.Journal of cell communication and signaling · 2026Article
- Erythritol Exacerbates DSS-Induced Colitis and Influences Behavioral Responses in Mice Through Gut Microbiota and Metabolic Alterations.Microorganisms · 2026Article
- Sevoflurane Alleviates Myocardial Ischemia-Reperfusion Injury via the HMGB1/ACSL4 Pathway to Suppress Ferroptosis.Journal of biochemical and molecular toxicology · 2026Article
- Cardiomyocyte-enriched OTUD5 alleviates septic cardiomyopathy by promoting NLRP3 deubiquitination and inhibiting NLRP3 inflammasome activation.Clinical and translational medicine · 2026Article
- HIF-1α enhances ferroptosis resistance in anaplastic thyroid carcinoma by suppressing ACSL4-mediated lipid metabolic homeostasis.Cellular & molecular biology letters · 2026Article
- Inhibition of the 4-hydroxynonenal-regulated JNK/c-Jun pathway improves bleomycin-induced lung fibrosis.Biomedical journal · 2026Article
- Probiotic interventions maintain intestinal barrier function and alleviate necrotizing enterocolitis by inhibiting ferroptosis in intestinal PMN-MDSCs.Cell death & disease · 2026Article
- Cysteine imaging reveals early redox dysregulation and identifies gnetol as a ferroptosis-modulating agent in doxorubicin cardiotoxicity.Redox biology · 2026Article
- TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis.Circulation · 2026Article
- Chaperone-Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite the development of advanced technologies for interventional coronary reperfusion after myocardial infarction, a substantial number of patients experience high mortality due to myocardial ischemia-reperfusion (MI/R) injury. An in-depth understanding of the mechanisms underlying MI/R injury can provide crucial strategies for mitigating myocardial damage and improving patient survival. Here, it is discovered that the 4-hydroxy-2-nonenal (4-HNE) accumulates during MI/R, accompanied by high rates of myocardial ferroptosis. The loss-of-function of aldehyde dehydrogenase 2 (ALDH2), which dissipates 4-HNE, aggravates myocardial ferroptosis, whereas the activation of ALDH2 mitigates ferroptosis. Mechanistically, 4-HNE targets glutathione peroxidase 4 (GPX4) for K48-linked polyubiquitin-related degradation, which 4-HNE-GPX4 axis commits to myocyte ferroptosis and forms a positive feedback circuit. 4-HNE blocks the interaction between GPX4 and ovarian tumor (OTU) deubiquitinase 5 (OTUD5) by directly carbonylating their cysteine residues at C93 of GPX4 and C247 of OTUD5, identifying OTUD5 as the novel deubiquitinase for GPX4. Consequently, the elevation of OTUD5 deubiquitinates and stabilizes GPX4 to reverse 4-HNE-induced ferroptosis and alleviate MI/R injury. The data unravel the mechanism of 4-HNE in GPX4-dependent ferroptosis and identify OTUD5 as a novel therapeutic target for the treatment of MI/R injury.
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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.