Defining Cancer Cell Bioenergetic Profiles Using a Dual Organelle-Oriented Chemosensor Responsive to pH Values and Electropotential Changes
Defining Cancer Cell Bioenergetic Profiles Using a Dual Organelle-Oriented Chemosensor Responsive to pH Values and Electropotential Changes
复制标题
使用响应 pH 值和电位变化的双细胞器导向化学传感器定义癌细胞生物能特征
DOI：
10.1021/acs.analchem.7b01934
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发表时间：
2017
影响因子：
7.4
通讯作者：
Han Shoufa
中科院分区：
文献类型：
--
作者：
Xue Zhongwei;Zhao Hu;Liu Jian;Han Jiahuai;Han Shoufa
细胞命运在很大程度上是由不同类型的细胞器的组合活动形成的，这些细胞器通常具有屈服于病理诱导物的功能关键参数。我们在此报告的细胞生物能谱的分析与双细胞器导向的化学传感器（RC-AMI），分区在线粒体中，以提供蓝色荧光和溶酶体中，以提供红色荧光。响应于溶酶体pH和线粒体跨膜电位（Δ Δ μ m）（两个对细胞生物能量学至关重要的参数），RC-AMI能够实现溶酶体酸度和Δ μ m的双色报告，揭示了在癌细胞中上调的Δ μ m和Δ μ m不平衡显著地改变，有利于Δ μ mor溶酶体酸度，而在饥饿细胞中该趋势被逆转。作为经典的同源细胞器特异性传感器的补充，这种双重细胞器导向和荧光响应探针提供了一种新的工具来检测溶酶体酸度和线粒体Δ m之间的不平衡，这是癌症生物能量学的关键指标。
Cell fate is largely shaped by combined activity of different types of organelles, which often feature functionally critical parameters that succumb to pathological inducers. We herein report the analysis of cell bioenergetic profiles with a dual organelle-oriented chemosensor (RC-AMI), partitioning in mitochondria to give blue fluorescence and in lysosomes to give red fluorescence. Responsive to lysosomal pH and mitochondrial transmembrane potential (ΔΨm), two parameters crucial to cell bioenergetics, RC-AMI enables dual colored reporting of lysosomal acidity and ΔΨm, revealing upregulated ΔΨmand imbalance dramatically shifted favoring ΔΨmover lysosomal acidity in cancer cells whereas the tendency is reversed in starved cells. Complementing classical homo-organelle-specific sensors, this dual organelle-oriented and fluorescently responsive probe offers a new tool to detect imbalance between lysosomal acidity and mitochondrial ΔΨm, an index critical for cancer bioenergetics.