ArticleFree radical biology & medicine2023
Membrane regulation of 15LOX-1/PEBP1 complex prompts the generation of ferroptotic signals, oxygenated PEs.
Article in Free radical biology & medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Exploring Ferroptosis: A Key Mechanism in Respiratory System Diseases and its Therapeutic Potential.Applied biochemistry and biotechnology · 2026Review
- 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
- Targeting ferroptosis in osteoporosis: mechanisms and natural products therapies.Frontiers in pharmacology · 2026Review
- NFS1 Plays a Critical Role in Regulating Ferroptosis Homeostasis.Biomolecules · 2025Review
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- 15-Lipoxygenase-dependent radiomitigation by NORedox biology · 2025Article
- A new perspective on iron-dependent cell death: PRDX-1-mediated ferroptosis in tumor cells.Apoptosis : an international journal on programmed cell death · 2025Review
- The presence of substrate warrants oxygen access tunnels toward the catalytic site of lipoxygenases.Redox biology · 2025Article
- PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification.Diagnostics (Basel, Switzerland) · 2025Article
- LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid.Translational oncology · 2025Article
- Epitranscriptomic mechanisms and implications of RNA mTheranostics · 2025Review
- The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.Neurochemical research · 2024Review
- Insights into the pathogenesis of gestational and hepatic diseases: the impact of ferroptosis.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
11 authors.
Funding
Abstract
Ferroptosis is a regulated form of cell death, the mechanism of which is still to be understood. 15-lipoxygenase (15LOX) complex with phosphatidylethanolamine (PE)-binding protein 1 (PEBP1) catalyzes the generation of pro-ferroptotic cell death signals, hydroperoxy-polyunsaturated PE. We focused on gaining new insights into the molecular basis of these pro-ferroptotic interactions using computational modeling and liquid chromatography-mass spectrometry experiments. Simulations of 15LOX-1/PEBP1 complex dynamics and interactions with lipids revealed that association with the membrane triggers a conformational change in the complex. This conformational change facilitates the access of stearoyl/arachidonoyl-PE (SAPE) substrates to the catalytic site. Furthermore, the binding of SAPE promotes tight interactions within the complex and induces further conformational changes that facilitate the oxidation reaction. The reaction yields two hydroperoxides as products, 15-HpETE-PE and 12-HpETE-PE, at a ratio of 5:1. A significant effect of PEBP1 is observed only on the predominant product. Moreover, combined experiments and simulations consistently demonstrate the significance of PEBP1 P112E mutation in generating ferroptotic cell death signals.
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