当前位置: X-MOL 学术FEBS Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A switchable ceramide transfer protein for dissecting the mechanism of ceramide‐induced mitochondrial apoptosis
FEBS Letters ( IF 3.5 ) Pub Date : 2020-10-26 , DOI: 10.1002/1873-3468.13956
Amrita Jain 1 , Shashank Dadsena 1 , Joost C. M. Holthuis 1
Affiliation  

Mitochondrial translocation of ceramides triggers Bax‐dependent apoptosis. To elucidate how ceramides activate Bax and commit cells to death, we developed a switchable version of the ceramide transfer protein CERT, sCERT. Upon its drug‐induced recruitment to mitochondria, sCERT retains the ability to bind VAP proteins in the ER and catalyzes mitochondrial import of externally added fluorescent ceramides. Mitochondrial recruitment of sCERT also triggers mitochondrial translocation of Bax. The ability of mitochondria‐bound sCERT to mediate ceramide import and Bax translocation requires both its START domain and ongoing ceramide biosynthesis. These data extend our previous finding that mistargeting of ER ceramides to mitochondria specifically activates Bax and establish sCERT as a novel tool to dissect the underlying mechanism in a time‐resolved manner.

中文翻译:

一种可转换的神经酰胺转移蛋白,用于剖析神经酰胺诱导的线粒体凋亡机制

神经酰胺的线粒体易位触发 Bax 依赖性细胞凋亡。为了阐明神经酰胺如何激活 Bax 并使细胞死亡,我们开发了神经酰胺转移蛋白 CERT 的可切换版本,即 sCERT。在药物诱导的线粒体募集后,sCERT 保留了结合内质网中 VAP 蛋白的能力,并催化外部添加的荧光神经酰胺的线粒体输入。sCERT 的线粒体募集也会触发 Bax 的线粒体易位。线粒体结合的 sCERT 介导神经酰胺输入和 Bax 易位的能力需要其 START 结构域和持续的神经酰胺生物合成。
更新日期:2020-10-26
down
wechat
bug