ArticleAngewandte Chemie (International ed. in English)2024
Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death.
Article in Angewandte Chemie (International ed. in English), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 44 citations in OpenAlex.
- Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).International journal of molecular medicine · 2026Review
- A Ferrous-Supply-Regenerating Lipid Nanoparticle Integrating RNAi Induces Ferroptosis for Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Subtype-specific mechanisms of lipid metabolism in gynecological malignancies and novel targeted intervention strategies (Review).Oncology letters · 2026Review
- PLA2G2F suppresses ferroptosis through phospholipid remodeling.Nature structural & molecular biology · 2026Article
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- Tumor cell ferroptosis in antitumor immunity and immunotherapy efficacy.Journal for immunotherapy of cancer · 2026Review
- Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits.Metabolites · 2026Article
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- The biphasic interactions between ferroptosis and oxidative stress: from molecular mechanisms to disease interventions.Molecular biology reports · 2026Review
- Dual lipid modulation overcomes ferroptosis resistance in high-risk neuroblastoma.Cell death and differentiation · 2026Article
- Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.Antioxidants (Basel, Switzerland) · 2026Review
- Ferroptosis in metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Lipid remodeling and ferroptosis in phosphatidylcholine-mediated tumor-stroma crosstalk.Frontiers in molecular biosciences · 2026Review
- The dual roles of ferroptosis in digestive tract tumors: mechanisms, microenvironment regulation, and therapeutic integration with emphasis on immune interactions.Frontiers in immunology · 2026Review
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Review
- Emerging Roles of Ferroptosis in Skin Pathophysiology.The Journal of investigative dermatology · 2025Review
- Allosteric Autoregulation of Ferroptosis Suppressor Protein 1 Activity by its N-myristoylated Tail.Journal of molecular biology · 2025Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 3 countries.
Funding
Abstract
The vast majority of membrane phospholipids (PLs) include two asymmetrically positioned fatty acyls: oxidizable polyunsaturated fatty acids (PUFA) attached predominantly at the sn2 position, and non-oxidizable saturated/monounsaturated acids (SFA/MUFA) localized at the sn1 position. The peroxidation of PUFA-PLs, particularly sn2-arachidonoyl(AA)- and sn2-adrenoyl(AdA)-containing phosphatidylethanolamines (PE), has been associated with the execution of ferroptosis, a program of regulated cell death. There is a minor subpopulation (≈1-2 mol %) of doubly PUFA-acylated phospholipids (di-PUFA-PLs) whose role in ferroptosis remains enigmatic. Here we report that 15-lipoxygenase (15LOX) exhibits unexpectedly high pro-ferroptotic peroxidation activity towards di-PUFA-PEs. We revealed that peroxidation of several molecular species of di-PUFA-PEs occurred early in ferroptosis. Ferrostatin-1, a typical ferroptosis inhibitor, effectively prevented peroxidation of di-PUFA-PEs. Furthermore, co-incubation of cells with di-AA-PE and 15LOX produced PUFA-PE peroxidation and induced ferroptotic death. The decreased contents of di-PUFA-PEs in ACSL4 KO A375 cells was associated with lower levels of di-PUFA-PE peroxidation and enhanced resistance to ferroptosis. Thus, di-PUFA-PE species are newly identified phospholipid peroxidation substrates and regulators of ferroptosis, representing a promising therapeutic target for many diseases related to ferroptotic death.
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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.