Determination of the Subcellular Localization and Mechanism of Action of Ferrostatins in Suppressing Ferroptosis

Ferroptosis is a form of nonapoptotic cell death characterized by the unchecked accumulation of lipid peroxides. Ferrostatin-1 and its analogs (ferrostatins) specifically prevent ferroptosis in multiple contexts, but many aspects of their molecular mechanism of action remain poorly described. Here,...

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Published inACS chemical biology Vol. 13; no. 4; pp. 1013 - 1020
Main Authors Gaschler, Michael M, Hu, Fanghao, Feng, Huizhong, Linkermann, Andreas, Min, Wei, Stockwell, Brent R
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 20.04.2018
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ISSN1554-8929
1554-8937
1554-8937
DOI10.1021/acschembio.8b00199

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Summary:Ferroptosis is a form of nonapoptotic cell death characterized by the unchecked accumulation of lipid peroxides. Ferrostatin-1 and its analogs (ferrostatins) specifically prevent ferroptosis in multiple contexts, but many aspects of their molecular mechanism of action remain poorly described. Here, we employed stimulated Raman scattering (SRS) microscopy coupled with small vibrational tags to image the distribution of ferrostatins in cells and found that they accumulate in lysosomes, mitochondria, and the endoplasmic reticulum. We then evaluated the functional relevance of lysosomes and mitochondria to ferroptosis suppression by ferrostatins and found that neither is required for effective ferroptosis suppression.
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ISSN:1554-8929
1554-8937
1554-8937
DOI:10.1021/acschembio.8b00199