[HTML][HTML] Ferroptosis: an iron-dependent form of nonapoptotic cell death

SJ Dixon, KM Lemberg, MR Lamprecht, R Skouta… - cell, 2012 - cell.com
SJ Dixon, KM Lemberg, MR Lamprecht, R Skouta, EM Zaitsev, CE Gleason, DN Patel…
cell, 2012cell.com
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 …
Summary
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 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.
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