Ferroptosis: an iron-dependent form of nonapoptotic cell death
| Autor: | Rachid Skouta, Caroline E Gleason, Barclay Morrison, Brent R. Stockwell, Wan Seok Yang, Eleina M. Zaitsev, Scott J. Dixon, Michael R. Lamprecht, Andras J. Bauer, Darpan N Patel, Kathryn M. Lemberg, Alexandra M. Cantley |
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| Rok vydání: | 2012 |
| Předmět: |
Programmed cell death
Iron Cell Glutamic Acid Biology SLC7A11 In Vitro Techniques Phenylenediamines Hippocampus Article General Biochemistry Genetics and Molecular Biology Piperazines 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Animals Humans 030304 developmental biology 0303 health sciences Cyclohexylamines Cell Death Biochemistry Genetics and Molecular Biology(all) Autophagy Neurodegeneration Fibroblasts medicine.disease Lipid Metabolism 3. Good health Cell biology Rats medicine.anatomical_structure Apoptosis 030220 oncology & carcinogenesis Cancer cell biology.protein Reactive Oxygen Species Intracellular |
| Zdroj: | Cell. 149(5) |
| ISSN: | 1097-4172 |
| Popis: | SummaryNonapoptotic 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 xc−), 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.PaperFlick |
| Databáze: | OpenAIRE |
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