Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death,Angewandte Chemie International Edition

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Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2024-01-17 , DOI: 10.1002/anie.202314710
Svetlana N Samovich _{1,

2} , Karolina Mikulska-Ruminska ₃ , Haider H Dar ₂ , Yulia Y Tyurina ₂ , Vladimir A Tyurin ₂ , Austin B Souryavong ₂ , Alexander A Kapralov ₂ , Andrew A Amoscato ₂ , Ofer Beharier ₄ , S Ananth Karumanchi ₅ , Claudette M St Croix ₆ , Xin Yang ₇ , Theodore R Holman ₈ , Andrew P VanDemark ₉ , Yoel Sadovsky _{10,

11} , Rama K Mallampalli ₁₂ , Sally E Wenzel ₂ , Wei Gu _{7,

13} , Yuri L Bunimovich ₁₄ , Ivet Bahar ₁₅ , Valerian E Kagan _{2,

16,

17,

18} , Hülya Bayir _{1,

2,

19}

Affiliation

Department of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University in Torun, Torun, PL87100, Poland.
Obstetrics and Gynecology Division, Hadassah Medical Center, Faculty of Medicine of the Hebrew University of Jerusalem, 97654, Jerusalem, Israel.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Laufer Center for Physical and Quantitative Biology, Laufer Center, Z-5252, Stony Brook University, Stony Brook, NY 11794, USA.
Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Critical Care Medicine, Safar Center for Resuscitation Research, Children's Neuroscience Institute, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Doubly polyunsaturated phospholipids are present in biomembranes, albeit at very low abundancies. Their specific function is not known. We discovered that 15-lipoxygenase catalyzes oxygenation of these phospholipids at the same high rate as free fatty acids and yield 15-hydroperoxy-products which act as pro-ferroptotic signals of cell death.

中文翻译：

15-脂氧合酶对二多不饱和花生四烯酰/肾上腺酰磷脂酰乙醇胺的惊人高活性产生铁死亡细胞死亡的过氧化信号

双多不饱和磷脂存在于生物膜中，尽管丰度非常低。它们的具体功能尚不清楚。我们发现 15-脂氧合酶以与游离脂肪酸相同的高速率催化这些磷脂的氧合，并产生 15-氢过氧产物，作为细胞死亡的促铁死亡信号。

更新日期：2024-01-17

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