ArticleProceedings of the National Academy of Sciences of the United States of America2020
PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 113 citations in OpenAlex.
- PEBP1 Regulates Ferroptosis in Acute Glaucoma: Targeted Therapy Using Engineered Exosomes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- PEBP1 inhibition as a therapeutic target for neurological recovery in ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Ferroptosis as an Emerging Therapeutic Target in Allergic Diseases.Drug design, development and therapy · 2026Review
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Acupuncture Treatment Alleviating Pyroptosis on Asthma Inflammation in Mice via Micro-RNA-223/NLRP3 Pathway.Mediators of inflammation · 2026Article
- Convergent death programs in chronic obstructive pulmonary disease: how pyroptotic and ferroptotic crosstalk reshapes therapeutic paradigms.Frontiers in immunology · 2026Review
- Emerging immune networks and targeted strategies in T2 asthma.Frontiers in immunology · 2026Review
- Association Between Ferritinophagy and M1 Macrophage Polarization During the Acute Phase of Childhood Allergic Asthma.Journal of inflammation research · 2026Article
- Integrating Bioinformatics and Experimental Validation Identifies SCD as a Ferroptosis-Related Immune Regulator and Therapeutic Target in Crohn's Disease.International journal of molecular sciences · 2025Article
- Stimulator of Interferon Genes Regulates Ferroptosis and Airway Inflammation via acyl-CoA Synthetase Long-Chain Family Member 4 in Asthmatic Mice.Inflammation · 2025Article
- Emerging dual role of ferroptosis in lung cancer (Review).Oncology reports · 2025Review
- Review
- Role of Ferroptosis on Lung Epithelial Cells in Disease Progression and Treatment: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- MTOR signaling regulates the development of airway mucous cell metaplasia associated with severe asthma.JCI insight · 2025Article
- Key genes and processes affected by atorvastatin treatment in mouse diaphragm muscle.Archives of toxicology · 2025Article
- PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification.Diagnostics (Basel, Switzerland) · 2025Article
- Clinical and mechanistic advancements in aspirin exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2025Review
- Cell death crosstalk in respiratory diseases: unveiling the relationship between pyroptosis and ferroptosis in asthma and COPD.Molecular and cellular biochemistry · 2025Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Temporally harmonized elimination of damaged or unnecessary organelles and cells is a prerequisite of health. Under Type 2 inflammatory conditions, human airway epithelial cells (HAECs) generate proferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamines (HpETE-PEs) as proximate death signals. Production of 15-HpETE-PE depends on activation of 15-lipoxygenase-1 (15LO1) in complex with PE-binding protein-1 (PEBP1). We hypothesized that cellular membrane damage induced by these proferroptotic phospholipids triggers compensatory prosurvival pathways, and in particular autophagic pathways, to prevent cell elimination through programmed death. We discovered that PEBP1 is pivotal to driving dynamic interactions with both proferroptotic 15LO1 and the autophagic protein microtubule-associated light chain-3 (LC3). Further, the 15LO1-PEBP1-generated ferroptotic phospholipid, 15-HpETE-PE, promoted LC3-I lipidation to stimulate autophagy. This concurrent activation of autophagy protects cells from ferroptotic death and release of mitochondrial DNA. Similar findings are observed in Type 2 Hi asthma, where high levels of both 15LO1-PEBP1 and LC3-II are seen in HAECs, in association with low bronchoalveolar lavage fluid mitochondrial DNA and more severe disease. The concomitant activation of ferroptosis and autophagy by 15LO1-PEBP1 complexes and their hydroperoxy-phospholipids reveals a pathobiologic pathway relevant to asthma and amenable to therapeutic targeting.
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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.