Artificially inducing close apposition of endoplasmic reticulum and mitochondria induces mitochondrial fragmentation.
Artificially inducing close apposition of endoplasmic reticulum and mitochondria induces mitochondrial fragmentation.
复制标题
人工诱导内质网和线粒体紧密并置会导致线粒体断裂。
DOI：
10.1101/005645
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Miller V
中科院分区：
文献类型：
--
作者：
Miller V
线粒体分裂和分裂的循环是正常细胞生理所必需的。控制这些过程的机制的缺陷导致神经退行性疾病。当我们开始了解驱动裂变的机制时，我们对这一事件的时空控制的知识是缺乏的。在这里，我们使用雷帕霉素诱导的异源二聚化系统，包括内质网和线粒体跨膜组分，使内质网膜与线粒体接近。我们表明，这种人工膜的附着足以导致线粒体快速断裂。由此产生的线粒体片段在光漂白后使用荧光恢复显示为不同的实体。我们还发现这些片段保留了线粒体膜电位。相反，外周内质网出口蛋白TFG的诱导拴系不会导致线粒体断裂，这表明需要两个膜非常接近。
Cycles of mitochondrial fission and fission are essential for normal cell physiology. Defects in the machinery controlling these processes lead to neurodegenerative disease. While we are beginning to understand the machinery that drives fission, our knowledge of the spatial and temporal control of this event is lacking. Here we use a rapamycin-inducible heterodimerization system comprising both ER and mitochondrial transmembrane components to bring the ER membrane into close physical proximity with mitochondria. We show that this artificial apposition of membranes is sufficient to cause rapid mitochondrial fragmentation. Resulting mitochondrial fragments are shown to be distinct entities using fluorescence recovery after photobleaching. We also show that these fragments retain a mitochondrial membrane potential. In contrast, inducible tethering of the peripheral ER exit site protein TFG does not cause mitochondrial fragmentation suggesting that very close apposition of the two membranes is required.