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

被引:265
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
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
收藏
页码:1013 / 1020
页数:8
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