Drp1 以 GTPase 非依赖的方式管状化内质网。
Drp1 Tubulates the ER in a GTPase-Independent Manner.
机构信息
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
出版信息
Mol Cell. 2020 Nov 19;80(4):621-632.e6. doi: 10.1016/j.molcel.2020.10.013. Epub 2020 Nov 4.
Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
线粒体是高度动态的细胞器，不断生长、分裂和融合。线粒体的分裂对人类健康至关重要。在线粒体分裂过程中，机械鸟嘌呤核苷酸三磷酸酶（GTPase）相关蛋白 dynamin （Drp1）在内质网（ER）-线粒体接触部位将线粒体切开，其中外周 ER 小管与线粒体相互作用。在这里，我们报告 Drp1 直接塑造人类和小鼠细胞中的外周 ER 小管。这种 ER 塑形活性不依赖于 GTP 水解，位于一个高度保守的 18 个氨基酸肽（称为 D-十八肽）中，该肽预测形成一个两亲性α螺旋。合成的 D-十八肽在体外的脂质体和细胞中的 ER 中形成小管。由 Drp1 形成的 ER 小管通过促进 ER-线粒体相互作用来促进线粒体分裂。因此，Drp1 在线粒体分裂过程中充当双功能蛋白，具有 ER 小管化和机械 GTPase 活性。
Zotero 插件