Optogenetic apoptosis: light-triggered cell death.
Optogenetic apoptosis: light-triggered cell death.
复制标题
光遗传凋亡：光触发的细胞死亡。
DOI：
10.1002/anie.201506346
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发表时间：
2015-10-05
期刊：
影响因子：
--
通讯作者：
Lawrence DS
中科院分区：
文献类型：
--
作者：
Hughes RM;Freeman DJ;Lamb KN;Pollet RM;Smith WJ;Lawrence DS
已经设计了促进光诱导的细胞凋亡的光遗传学Bax。我们证明，线粒体招聘的基因编码的光响应Bax的结果在线粒体蛋白的释放，下游半胱天冬酶3裂解，细胞形态的变化，并最终细胞死亡。关键磷酸化残基的突变或C-末端的修饰减轻了由于Bax过表达引起的凋亡的背景水平（深色）。使用一系列已知干扰程序性细胞死亡中的各个步骤的小分子来探索光遗传学细胞凋亡介导的细胞凋亡的机制。光遗传Bax似乎形成了一个线粒体凋亡诱导的通道类似于内源性Bax。
An optogenetic Bax has been designed that facilitates light-induced apoptosis. We demonstrate that mitochondrial recruitment of a genetically encoded light-responsive Bax results in the release of mitochondrial proteins, downstream caspase 3 cleavage, changes in cellular morphology, and ultimately cell death. Mutagenesis of a key phosphorylatable residue or modification of the C-terminus mitigates background levels (dark) of apoptosis due to Bax overexpression. The mechanism of optogenetic Bax-mediated apoptosis was explored using a series of small molecules known to interfere with various steps in programmed cell death. Optogenetic Bax appears to form a mitochondrial apoptosis-induced channel analogous to that of endogenous Bax.