A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed.
A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed.
复制标题
DOI：
10.1016/j.celrep.2015.10.042
复制
发表时间：
2015-12-01
期刊：
影响因子：
8.8
通讯作者：
Hergenrother PJ
中科院分区：
文献类型：
--
作者：
Palchaudhuri R;Lambrecht MJ;Botham RC;Partlow KC;van Ham TJ;Putt KS;Nguyen LT;Kim SH;Peterson RT;Fan TM;Hergenrother PJ
细胞凋亡通常被认为是一个需要几个小时的过程，而非程序性的细胞死亡可以在几分钟内发生。我们的发现挑战了细胞凋亡的耗时性质，因为我们描述了一种名为Raptinal的小分子的发现和表征，它在几分钟内在多个细胞系中启动内部途径caspase依赖的细胞凋亡。与一组机械上不同的凋亡刺激相比较，显示Raptina诱导的细胞凋亡以无与伦比的速度进行。这种快速的表型使人们能够确定线粒体电压依赖性阴离子通道功能、线粒体膜电位/耦合呼吸以及线粒体复合体I、III和IV功能在诱导细胞凋亡中的关键作用。Raptina在整个生物体中的应用证明了其在体内研究细胞凋亡的各种应用的有效性。总体而言，快速诱导凋亡是一种强大的工具，将在各种环境中使用，以进一步深入了解细胞凋亡的机制。
Apoptosis is generally believed to be a process that requires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the critical roles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility to study apoptosis in vivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery.