Organelle-specific analysis of labile Fe(II) during ferroptosis by using a cocktail of various colour organelle-targeted fluorescent probes
Organelle-specific analysis of labile Fe(II) during ferroptosis by using a cocktail of various colour organelle-targeted fluorescent probes
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DOI：
10.1039/c8mt00212f
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发表时间：
2019-01-01
期刊：
影响因子：
3.4
通讯作者：
Nagasawa, Hideko
中科院分区：
文献类型：
--
作者：
Hirayama, Tasuku;Miki, Ayaji;Nagasawa, Hideko
铁下垂是一种新兴的依赖铁的细胞死亡模式。不幸的是，细胞器不稳定铁（II）在细胞氧化损伤和致死性中的作用尚未得到详细的分析，这主要是由于缺乏有效的方法来可视化目标细胞器上的不稳定铁（II）。我们最近报道了一系列铁（II）选择性荧光探针，即Ac-MtFluNox， lyso - ronox和ER- sirhonox，它们分别可以特异性检测线粒体，溶酶体和内质网（ER）中的铁（II）。这些探针显示出相似的反应速率和不同颜色和细胞内分布的关闭/打开对比，能够同时进行多色成像，从而可以监测每个目标细胞器上的不稳定铁（II）水平。在本文中，通过使用这些探针的混合物，我们成功地可视化了在erastin诱导HT1080细胞死亡之前，溶酶体和内质网中不稳定Fe（II）的异常升高，erastin是铁凋亡的诱导剂。
Ferroptosis is an emerging type of cell death mode that is dependent on iron. Unfortunately, the detailed analysis of the function of organelle labile Fe(II) in oxidative damage and lethality of the cells has not been demonstrated so far, mainly due to the lack of efficient methods to visualize labile Fe(II) at the targeted organelles. We have recently reported a series of Fe(II)-selective fluorescent probes, i.e., Ac-MtFluNox, Lyso-RhoNox, and ER-SiRhoNox, which can detect Fe(II) specifically in the mitochondria, lysosomes, and endoplasmic reticulum (ER), respectively. These probes demonstrate similar reaction rates and off/on contrasts with various colours and intracellular distributions, enabling simultaneous multi-colour imaging that allows the monitoring of labile Fe(II) levels at each targeted organelle. In this paper, by using a cocktail of these probes, we successfully visualised the aberrant elevation of labile Fe(II) in the lysosomes and ER prior to HT1080 cell death induced by erastin, which is an inducer of ferroptosis.