Document Detail


Ferroptosis: an iron-dependent form of nonapoptotic cell death.
MedLine Citation:
PMID:  22632970     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration.
Authors:
Scott J Dixon; Kathryn M Lemberg; Michael R Lamprecht; Rachid Skouta; Eleina M Zaitsev; Caroline E Gleason; Darpan N Patel; Andras J Bauer; Alexandra M Cantley; Wan Seok Yang; Barclay Morrison; Brent R Stockwell
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell     Volume:  149     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-07-30     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1060-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biological Sciences, Columbia University, 550 West 120th Street, Northwest Corner Building, MC 4846, New York, NY 10027, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death* / drug effects
Cyclohexylamines / pharmacology
Fibroblasts / cytology,  metabolism
Glutamic Acid / metabolism
Hippocampus / cytology
Humans
Iron / metabolism*
Lipid Metabolism
Neoplasms / pathology
Phenylenediamines / pharmacology
Piperazines / metabolism
Rats
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
5R01CA097061/CA/NCI NIH HHS; 5R01GM085081/GM/NIGMS NIH HHS; R01 CA097061/CA/NCI NIH HHS; R01 CA161061/CA/NCI NIH HHS; R01 GM085081/GM/NIGMS NIH HHS; R01CA161061/CA/NCI NIH HHS; //Canadian Institutes of Health Research; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Cyclohexylamines; 0/Phenylenediamines; 0/Piperazines; 0/Reactive Oxygen Species; 0/erastin; 0/ferrostatin-1; 56-86-0/Glutamic Acid; 7439-89-6/Iron
Comments/Corrections
Comment In:
Cell. 2012 May 25;149(5):963-5   [PMID:  22632964 ]

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