Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Dixon SJ,Lemberg KM,Lamprecht MR,Skouta R,Zaitsev EM,Gleason CE,Patel DN,Bauer AJ,Cantley AM,Yang WS,Morrison B 3rd,Stockwell BRdoi
10.1016/j.cell.2012.03.042subject
Has Abstractpub_date
2012-05-25 00:00:00pages
1060-72issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(12)00520-Xjournal_volume
149pub_type
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