A guideline on the molecular ecosystem regulating ferroptosis

Enyong Dai; Xin Chen; Andreas Linkermann; Xuejun Jiang; Rui Kang; Valerian E Kagan; Hülya Bayir; Wan Seok Yang; Ana J Garcia-Saez; Maria S Ioannou; Tobias Janowitz; Qitao Ran; Wei Gu; Boyi Gan; Dmitri V Krysko; Xiaofeng Zhu; Jiayi Wang; Stefan Krautwald; Shinya Toyokuni; Yangchun Xie; Florian R Greten; Qing Yi; Joel Schick; Jiao Liu; Dmitry I Gabrilovich; Jinbao Liu; Herbert J Zeh; Donna D Zhang; Minghua Yang; Juan Iovanna; Manfred Kopf; Timon E Adolph; Jen-Tsan Chi; Changfeng Li; Hidenori Ichijo; Michael Karin; Vijay G Sankaran; Weiping Zou; Lorenzo Galluzzi; Ashley I Bush; Binghui Li; Gerry Melino; Eric H Baehrecke; Michael T Lotze; Daniel J Klionsky; Brent R Stockwell; Guido Kroemer; Daolin Tang

doi:10.1038/s41556-024-01360-8

A guideline on the molecular ecosystem regulating ferroptosis

Nat Cell Biol. 2024 Feb 29. doi: 10.1038/s41556-024-01360-8. Online ahead of print.

Authors

Enyong Dai¹, Xin Chen², Andreas Linkermann^{3

4}, Xuejun Jiang⁵, Rui Kang⁶, Valerian E Kagan⁷, Hülya Bayir⁸, Wan Seok Yang⁹, Ana J Garcia-Saez¹⁰, Maria S Ioannou¹¹, Tobias Janowitz¹², Qitao Ran¹³, Wei Gu¹⁴, Boyi Gan¹⁵, Dmitri V Krysko^{16

17}, Xiaofeng Zhu¹⁸, Jiayi Wang¹⁹, Stefan Krautwald²⁰, Shinya Toyokuni^{21

22}, Yangchun Xie²³, Florian R Greten^{24

25

26}, Qing Yi²⁷, Joel Schick²⁸, Jiao Liu²⁹, Dmitry I Gabrilovich³⁰, Jinbao Liu², Herbert J Zeh⁶, Donna D Zhang³¹, Minghua Yang^{32

33}, Juan Iovanna³⁴, Manfred Kopf³⁵, Timon E Adolph³⁶, Jen-Tsan Chi³⁷, Changfeng Li³⁸, Hidenori Ichijo³⁹, Michael Karin⁴⁰, Vijay G Sankaran^{41

42}, Weiping Zou⁴³, Lorenzo Galluzzi^{44

45

46}, Ashley I Bush⁴⁷, Binghui Li^{48

49

50}, Gerry Melino⁵¹, Eric H Baehrecke⁵², Michael T Lotze⁵³, Daniel J Klionsky⁵⁴, Brent R Stockwell⁵⁵, Guido Kroemer^{56

57

58}, Daolin Tang⁵⁹

Affiliations

¹ Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, China. daiey@jlu.edu.cn.
² Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
³ Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
⁴ Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
⁵ Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷ Department of Environmental Health, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Pediatrics, Columbia University, New York, NY, USA.
⁹ Department of Biological Sciences, St. John's University, New York, NY, USA.
¹⁰ Institute for Genetics, CECAD, University of Cologne, Cologne, Germany.
¹¹ Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
¹² Cold Spring Harbor Laboratory, New York, USA.
¹³ Department of Cell Systems and Anatomy, South Texas Veterans Health Care System, San Antonio, TX, USA.
¹⁴ Institute for Cancer Genetics, and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹⁵ Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁶ Cell Death Investigation and Therapy (CDIT) Laboratory, Department of Human Structure and Repair, Ghent University, Ghent, Belgium.
¹⁷ Cancer Research Institute Ghent, Ghent, Belgium.
¹⁸ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
¹⁹ Department of Clinical Laboratory, Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital and College of Medical Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁰ Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, Germany.
²¹ Department of Pathology and Biological Response, Nagoya University Graduate School of Medicine, Nagoya, Japan.
²² Center for Low-Temperature Plasma Sciences, Nagoya University, Nagoya, Japan.
²³ Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
²⁴ Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany.
²⁵ Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany.
²⁶ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁷ Houston Methodist Neal Cancer Center/Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas, USA.
²⁸ Genetics and Cellular Engineering Group, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum Munich, Neuherberg, Germany.
²⁹ DAMP Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³⁰ AstraZeneca, Early Oncology R&D, Gaithersburg, MD, USA.
³¹ Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA.
³² Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.
³³ Hunan Clinical Research Center of Pediatric Cancer, Changsha, China.
³⁴ Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, France.
³⁵ Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
³⁶ Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria.
³⁷ Department of Molecular Genetics and Microbiology Center for Applied Genomic Technologies, Duke University, Durham, NC, USA.
³⁸ Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China.
³⁹ Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
⁴⁰ Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
⁴¹ Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁴² Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴³ Departments of Surgery and Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴⁴ Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
⁴⁵ Sandra and Edward Meyer Cancer Center, New York, NY, USA.
⁴⁶ Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
⁴⁷ Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
⁴⁸ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
⁴⁹ Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
⁵⁰ Department of Cancer Cell Biology and National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
⁵¹ Department of Experimental Medicine, Tor Vergata University of Rome, Rome, Italy.
⁵² Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
⁵³ Departments of Surgery, Immunology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
⁵⁴ Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
⁵⁵ Department of Biological Sciences and Department of Chemistry, Columbia University, New York, NY, USA. bs2198@columbia.edu.
⁵⁶ Equipe labellisée par la Ligue contre le cancer, Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris, France. kroemer@orange.fr.
⁵⁷ Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. kroemer@orange.fr.
⁵⁸ Department of Biology, Institut du Cancer Paris CARPEM, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. kroemer@orange.fr.
⁵⁹ Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. daolin.tang@utsouthwestern.edu.

PMID: 38424270
DOI: 10.1038/s41556-024-01360-8

Abstract

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

Publication types

Review

Grants and funding

733 310030_170320/U.S. Department of Health & Human Services | National Institutes of Health (NIH)