2. Academic Validation
  3. Ferroptosis in health and disease

Ferroptosis in health and disease

  • Redox Biol. 2024 Sep:75:103211. doi: 10.1016/j.redox.2024.103211.
Carsten Berndt 1,  Hamed Alborzinia 2,  Vera Skafar Amen 3,  Scott Ayton 4,  Uladzimir Barayeu 5,  Alexander Bartelt 6,  Hülya Bayir 7,  Christina M Bebber 8,  Kivanc Birsoy 9,  Jan P Böttcher 10,  Simone Brabletz 11,  Thomas Brabletz 11,  Ashley R Brown 12,  Bernhard Brüne 13,  Giorgia Bulli 14,  Alix Bruneau 15,  Quan Chen 16,  Gina M DeNicola 17,  Tobias P Dick 18,  Ayelén Distéfano 19,  Scott J Dixon 20,  Jan B Engler 21,  Julia Esser-von Bieren 22,  Maria Fedorova 23,  José Pedro Friedmann Angeli 3,  Manuel A Friese 21,  Dominic C Fuhrmann 13,  Ana J García-Sáez 24,  Karolina Garbowicz 25,  Magdalena Götz 26,  Wei Gu 27,  Linda Hammerich 15,  Behrouz Hassannia 28,  Xuejun Jiang 29,  Aicha Jeridi 30,  Yun Pyo Kang 31,  Valerian E Kagan 32,  David B Konrad 33,  Stefan Kotschi 34,  Peng Lei 35,  Marlène Le Tertre 36,  Sima Lev 37,  Deguang Liang 29,  Andreas Linkermann 38,  Carolin Lohr 39,  Svenja Lorenz 40,  Tom Luedde 39,  Axel Methner 41,  Bernhard Michalke 42,  Anna V Milton 33,  Junxia Min 43,  Eikan Mishima 40,  Sebastian Müller 44,  Hozumi Motohashi 45,  Martina U Muckenthaler 36,  Shohei Murakami 45,  James A Olzmann 46,  Gabriela Pagnussat 19,  Zijan Pan 47,  Thales Papagiannakopoulos 48,  Lohans Pedrera Puentes 49,  Derek A Pratt 50,  Bettina Proneth 40,  Lukas Ramsauer 10,  Raphael Rodriguez 44,  Yoshiro Saito 51,  Felix Schmidt 41,  Carina Schmitt 33,  Almut Schulze 52,  Annemarie Schwab 11,  Anna Schwantes 13,  Mariluz Soula 9,  Benedikt Spitzlberger 53,  Brent R Stockwell 54,  Leonie Thewes 1,  Oliver Thorn-Seshold 33,  Shinya Toyokuni 55,  Wulf Tonnus 56,  Andreas Trumpp 57,  Peter Vandenabeele 58,  Tom Vanden Berghe 59,  Vivek Venkataramani 60,  Felix C E Vogel 52,  Silvia von Karstedt 61,  Fudi Wang 43,  Frank Westermann 25,  Chantal Wientjens 62,  Christoph Wilhelm 62,  Michele Wölk 23,  Katherine Wu 48,  Xin Yang 63,  Fan Yu 16,  Yilong Zou 64,  Marcus Conrad 65
Affiliations

Affiliations

  • 1 Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
  • 2 Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.
  • 3 Rudolf Virchow Zentrum, Center for Integrative and Translational Bioimaging - University of Würzburg, Germany.
  • 4 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
  • 5 Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ) Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany; Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 6 Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany; German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany.
  • 7 Department of Pediatrics, Columbia University, New York City, NY, USA.
  • 8 University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Translational Genomics, Cologne, Germany; CECAD Cluster of Excellence, University of Cologne, Cologne, Germany.
  • 9 Laboratory of Metabolic Regulation and Genetics, Rockefeller University, New York City, NY, USA.
  • 10 Institute of Molecular Immunology, School of Medicine, Technical University of Munich (TUM), Germany.
  • 11 Department of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander University of Erlangen-Nürnberg, Germany.
  • 12 Department of Biological Sciences, Columbia University, New York City, NY, USA.
  • 13 Institute of Biochemistry1-Pathobiochemistry, Goethe-Universität, Frankfurt Am Main, Germany.
  • 14 Department of Physiological Genomics, Ludwig-Maximilians-University, Munich, Germany.
  • 15 Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany.
  • 16 College of Life Sciences, Nankai University, Tianjin, China.
  • 17 Department of Metabolism and Physiology, Moffitt Cancer Center, Tampa, FL, USA.
  • 18 Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ) Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany.
  • 19 Instituto de Investigaciones Biológicas, CONICET, National University of Mar Del Plata, Argentina.
  • 20 Department of Biology, Stanford University, Stanford, CA, USA.
  • 21 Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Germany.
  • 22 Department of Immunobiology, Université de Lausanne, Switzerland.
  • 23 Center of Membrane Biochemistry and Lipid Research, University Hospital Carl Gustav Carus and Faculty of Medicine of TU Dresden, Germany.
  • 24 Institute for Genetics, CECAD, University of Cologne, Germany; Max Planck Institute of Biophysics, Frankfurt/Main, Germany.
  • 25 Division of Neuroblastoma Genomics, DKFZ, Heidelberg, Germany.
  • 26 Department of Physiological Genomics, Ludwig-Maximilians-University, Munich, Germany; Institute of Stem Cell Research, Helmholtz Center Munich, Germany.
  • 27 Institute for Cancer Genetics, And Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • 28 Department of Biomedical Sciences, University of Antwerp, Belgium.
  • 29 Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
  • 30 Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Germany, Member of the German Center for Lung Research (DZL).
  • 31 College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Republic of Korea.
  • 32 School of Public Health, University of Pittsburgh, PA, USA.
  • 33 Department of Pharmacy, Ludwig-Maximilians-University, Munich, Germany.
  • 34 Institute for Cardiovascular Prevention (IPEK), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
  • 35 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  • 36 Center for Translational Biomedical Iron Research, Heidelberg University, Germany.
  • 37 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • 38 Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany; Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
  • 39 Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
  • 40 Institute of Metabolism and Cell Death, Helmholtz Center Munich, Germany.
  • 41 Institute of Molecular Medicine, Johannes Gutenberg-Universität Mainz, Germany.
  • 42 Research Unit Analytical Biogeochemistry, Helmholtz Center Munich, Germany.
  • 43 School of Medicine, Zhejiang University, Hangzhou, China.
  • 44 Cellular and Chemical Biology, Institut Curie, Paris, France.
  • 45 Department of Gene Expression Regulation, Tohoku University, Sendai, Japan.
  • 46 Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • 47 School of Life Sciences, Westlake University, Hangzhou, China.
  • 48 Department of Pathology, Grossman School of Medicine, New York University, NY, USA.
  • 49 Institute for Genetics, CECAD, University of Cologne, Germany.
  • 50 Department of Chemistry and Biomolecular Sciences, University of Ottawa, Canada.
  • 51 Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • 52 Division of Tumour Metabolism and Microenvironment, DKFZ Heidelberg and DKFZ-ZMBH Alliance, Heidelberg, Germany.
  • 53 Department of Immunobiology, Université de Lausanne, Switzerland; Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany.
  • 54 Department of Biological Sciences, Columbia University, New York City, NY, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA; Department of Chemistry, Columbia University, New York, NY, USA.
  • 55 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Nagoya, Japan; Center for Integrated Sciences of Low-temperature Plasma Core Research (iPlasma Core), Tokai National Higher Education and Research System, Nagoya, Japan.
  • 56 Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany.
  • 57 Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
  • 58 VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • 59 Department of Biomedical Sciences, University of Antwerp, Belgium; VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  • 60 Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Germany.
  • 61 University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Translational Genomics, Cologne, Germany; CECAD Cluster of Excellence, University of Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne, Germany.
  • 62 Immunopathology Unit, Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University Hospital Bonn, University of Bonn, Germany.
  • 63 Institute for Cancer Genetics, And Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
  • 64 School of Life Sciences, Westlake University, Hangzhou, China; Westlake Four-Dimensional Dynamic Metabolomics (Meta4D) Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
  • 65 Institute of Metabolism and Cell Death, Helmholtz Center Munich, Germany. Electronic address: marcus.conrad@helmholtz-muenchen.de.
PMID: 38908072 DOI: 10.1016/j.redox.2024.103211
Abstract

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark of Ferroptosis is uncontrolled and overwhelming peroxidation of polyunsaturated fatty acids contained in membrane Phospholipids, which eventually leads to rupture of the plasma membrane. Ferroptosis is unique in that it is essentially a spontaneous, uncatalyzed chemical process based on perturbed iron and redox homeostasis contributing to the cell death process, but that it is nonetheless modulated by many metabolic nodes that impinge on the cells' susceptibility to Ferroptosis. Among the various nodes affecting Ferroptosis sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets for the treatment of numerous currently incurable diseases. Herein, the current members of a Germany-wide research consortium focusing on Ferroptosis research, as well as key external experts in Ferroptosis who have made seminal contributions to this rapidly growing and exciting field of research, have gathered to provide a comprehensive, state-of-the-art review on Ferroptosis. Specific topics include: basic mechanisms, in vivo relevance, specialized methodologies, chemical and pharmacological tools, and the potential contribution of Ferroptosis to disease etiopathology and progression. We hope that this article will not only provide established scientists and newcomers to the field with an overview of the multiple facets of Ferroptosis, but also encourage additional efforts to characterize further molecular pathways modulating Ferroptosis, with the ultimate goal to develop novel pharmacotherapies to tackle the various diseases associated with - or caused by - Ferroptosis.

Keywords

Cancer; Cell death; Iron; Ischemia/reperfusion; Lipid peroxidation; Neurodegeneration.

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