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

被引：282

作者：

Gaschler, Michael M. ^{[1
]}

Hu, Fanghao ^{[1
]}

Feng, Huizhong ^{[2
]}

Linkermann, Andreas ^{[3
]}

Min, Wei ^{[1
]}

Stockwell, Brent R. ^{[1
,2
]}

机构：

[1] Columbia Univ, Dept Chem, New York, NY 10027 USA

[2] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[3] Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Div Nephrol, Med Clin 3, D-01309 Dresden, Germany

来源：

ACS CHEMICAL BIOLOGY | 2018年 / 13卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CELL-DEATH;

D O I：

10.1021/acschembio.8b00199

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1013 / 1020

页数：8

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