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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

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 3rd, Brent R Stockwell

Cell. 2012 May 25;149(5):1060-72.

PMID: 22632970

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP347174054	Ferrostatin-1		347174-05-4	Price

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