Hughes Robert M, Freeman David J, Lamb Kelsey N, Pollet Rebecca M, Smith Weston J, Lawrence David S
Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599 (USA).
Angew Chem Int Ed Engl. 2015 Oct 5;54(41):12064-8. doi: 10.1002/anie.201506346. Epub 2015 Aug 25.
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 (dark) levels of apoptosis that result from 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.
一种光遗传学的Bax已被设计出来，它有助于光诱导的细胞凋亡。我们证明，一种基因编码的光响应性Bax在线粒体的募集导致线粒体蛋白的释放、下游半胱天冬酶-3的切割、细胞形态的改变，并最终导致细胞死亡。关键可磷酸化残基的诱变或C末端的修饰可减轻因Bax过表达导致的背景（黑暗）水平的细胞凋亡。使用一系列已知可干扰程序性细胞死亡各个步骤的小分子来探索光遗传学Bax介导的细胞凋亡机制。光遗传学Bax似乎形成了一个类似于内源性Bax的线粒体凋亡诱导通道。
