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lass="h3">Summary
Nonapoptotic forms of ce
ll death may faci
litate the聽se
lective e
limination of some tumor ce
lls or be activated in specific patho
logica
l states. The oncogenic RAS-se
lective
letha
l sma
ll mo
lecu
le erastin triggers a unique iron-dependent form of nonapoptotic ce
ll death that we term
ferroptosis. Ferroptosis is dependent upon intrace
llu
lar iron, but not other meta
ls, and is morpho
logica
lly, biochemica
lly, and genetica
lly distinct from apoptosis, necrosis, and autophagy. We identify the sma
ll mo
lecu
le ferrostatin-1 as a potent inhibitor of ferroptosis in cancer ce
lls and g
lutamate-induced ce
ll death in organotypic rat brain s
lices, suggesting simi
larities between these two processes. Indeed, erastin,
like g
lutamate, inhibits
cystine uptake by the
cystine/g
lutamate antiporter (system ), creating a void in the antioxidant defenses of the ce
ll and u
ltimate
ly
leading to聽iron-dependent, oxidative death. Thus, activation of ferroptosis resu
lts in the nonapoptotic destruction of certain cancer ce
lls, whereas inhibition of this process may protect organisms from neurodegeneration.
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