Xue Zhongwei, Zhao Hu, Liu Jian, Han Jiahuai, Han Shoufa
State Key Laboratory for Physical Chemistry of Solid Surfaces , Department of Chemical Biology , College of Chemistry and Chemical Engineering , The Key Laboratory for Chemical Biology of Fujian Province , The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation , Innovation Center for Cell Signalling Network , Xiamen University , Xiamen , 361005 , China . Email:
State Key Laboratory of Cellular Stress Biology , Innovation Center for Cell Signalling Network , School of Life Sciences , Xiamen University , Xiamen , 361005 , China.
Chem Sci. 2017 Mar 1;8(3):1915-1921. doi: 10.1039/c6sc04158b. Epub 2016 Nov 8.
Malfunctioning organelles are often difficult to probe with classical organelle-homing sensors owing to disruption of physiological organelle-probe affinity. We herein report the use of a responsive hetero-organelle partition and signal activable probe (RC-TPP) for detecting mitochondrial depolarization, a pathologically relevant event featuring loss of the electrical potentials across the mitochondrial membrane (Δ). Partitioned in mitochondria to give blue fluorescence, RC-TPP relocates into lysosomes upon mitochondrial depolarization and exhibits red fluorescence triggered by lysosomal acidity, enabling determination of autophagy relevant mitochondrial depolarization and the chronological sequence of mitochondrial depolarization and lysosomal neutralization in distinct cell death signalling pathways. As an alternative to classic homo-organelle specific molecular systems, this hetero-organelle responsive approach provides a new perspective from which to study dysfunctional organelles.
由于生理细胞器-探针亲和力的破坏，功能失调的细胞器通常难以用经典的细胞器靶向传感器进行探测。我们在此报告了一种响应性异细胞器分区和信号可激活探针（RC-TPP）用于检测线粒体去极化，这是一种与病理相关的事件，其特征是线粒体膜两侧的电势（Δ）丧失。RC-TPP在线粒体中分隔时发出蓝色荧光，线粒体去极化后重新定位到溶酶体中，并表现出由溶酶体酸性触发的红色荧光，从而能够确定自噬相关的线粒体去极化以及不同细胞死亡信号通路中线粒体去极化和溶酶体中和的时间顺序。作为经典的同细胞器特异性分子系统的替代方法，这种异细胞器响应方法为研究功能失调的细胞器提供了一个新的视角。
