Unsolved mysteries: How does lipid peroxidation cause ferroptosis?
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the danger...
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| description | Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases. |
| doi_str_mv | 10.1371/journal.pbio.2006203 |
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Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.2006203</identifier><identifier>PMID: 29795546</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis ; Autophagy ; Biochemistry ; Biology and Life Sciences ; Blood ; Cancer ; Cell Death ; Cell membranes ; Damage ; Diseases ; Drinking water ; Endoplasmic reticulum ; Ferroptosis ; Glutathione ; Glutathione peroxidase ; Glutathione Peroxidase - deficiency ; Health aspects ; Humans ; Iron ; Lipid Peroxidation ; Lipids ; Lipoxygenases - metabolism ; Maintenance ; Membranes ; Mortality ; Necroptosis ; Peroxidase ; Peroxidation ; Peroxides ; Physiology ; Rodents ; Unsolved Mystery</subject><ispartof>PLoS biology, 2018-05, Vol.16 (5), p.e2006203-e2006203</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Feng, Stockwell. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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deficiency</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Iron</topic><topic>Lipid Peroxidation</topic><topic>Lipids</topic><topic>Lipoxygenases - metabolism</topic><topic>Maintenance</topic><topic>Membranes</topic><topic>Mortality</topic><topic>Necroptosis</topic><topic>Peroxidase</topic><topic>Peroxidation</topic><topic>Peroxides</topic><topic>Physiology</topic><topic>Rodents</topic><topic>Unsolved Mystery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Huizhong</creatorcontrib><creatorcontrib>Stockwell, Brent R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ : Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Huizhong</au><au>Stockwell, Brent R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unsolved mysteries: How does lipid peroxidation cause ferroptosis?</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2018-05-24</date><risdate>2018</risdate><volume>16</volume><issue>5</issue><spage>e2006203</spage><epage>e2006203</epage><pages>e2006203-e2006203</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29795546</pmid><doi>10.1371/journal.pbio.2006203</doi><orcidid>https://orcid.org/0000-0002-3532-3868</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Autophagy Biochemistry Biology and Life Sciences Blood Cancer Cell Death Cell membranes Damage Diseases Drinking water Endoplasmic reticulum Ferroptosis Glutathione Glutathione peroxidase Glutathione Peroxidase - deficiency Health aspects Humans Iron Lipid Peroxidation Lipids Lipoxygenases - metabolism Maintenance Membranes Mortality Necroptosis Peroxidase Peroxidation Peroxides Physiology Rodents Unsolved Mystery |
| title | Unsolved mysteries: How does lipid peroxidation cause ferroptosis? |
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