Determination of the Subcellular Localization and Mechanism of Action of Ferrostatins in Suppressing Ferroptosis,ACS Chemical Biology

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Determination of the Subcellular Localization and Mechanism of Action of Ferrostatins in Suppressing Ferroptosis
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2018-03-07 00:00:00 , DOI: 10.1021/acschembio.8b00199
Michael M. Gaschler ₁ , Fanghao Hu ₁ , Huizhong Feng ₂ , Andreas Linkermann ₃ , Wei Min ₁ , Brent R. Stockwell _{1,

2}

Affiliation

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.

中文翻译：

Ferrostatin抑制肥大症的亚细胞定位及其作用机制的确定

Ferroptosis是非凋亡性细胞死亡的一种形式，其特征在于脂质过氧化物的无节制积累。Ferrostatin-1及其类似物（ferrostatins）在多种情况下均能特异性预防铁锈病，但对其分子作用机理的许多方面仍缺乏很好的描述。在这里，我们采用刺激的拉曼散射（SRS）显微镜和小的振动标记来成像铁递抑素在细胞中的分布，并发现它们在溶酶体，线粒体和内质网中积累。然后，我们评估了溶酶体和线粒体与Ferrostatin抑制肥大症的功能相关性，并发现两者均不需要有效抑制肥大症。

更新日期：2018-03-07

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