Otera Hidenori, Taira Yohsuke, Horie Chika, Suzuki Yurina, Suzuki Hiroyuki, Setoguchi Kiyoko, Kato Hiroki, Oka Toshihiko, Mihara Katsuyoshi
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
J Cell Biol. 2007 Dec 31;179(7):1355-63. doi: 10.1083/jcb.200702143. Epub 2007 Dec 24.
The central channel Tom40 of the preprotein translocase of outer membrane (TOM) complex is thought to be responsible for the import of virtually all preproteins synthesized outside the mitochondria. In this study, we analyze the topogenesis of the peripheral benzodiazepine receptor (PBR), which integrates into the mitochondrial outer membrane (MOM) through five hydrophobic transmembrane segments (TMSs) and functions in cholesterol import into the inner membrane. Analyses of in vitro and in vivo import into TOM component-depleted mitochondria reveal that PBR import (1) depends on the import receptor Tom70 but requires neither the Tom20 and Tom22 import receptors nor the import channel Tom40, (2) shares the post-Tom70 pathway with the C-tail-anchored proteins, and (3) requires factors of the mitochondrial intermembrane space. Furthermore, membrane integration of mitofusins and mitochondrial ubiquitin ligase, the MOM proteins with two and four TMSs, respectively, proceeds through the same initial pathway. These findings reveal a previously unidentified pathway of the membrane integration of MOM proteins with multiple TMSs.
外膜前体蛋白转运酶（TOM）复合物的中心通道Tom40被认为负责转运几乎所有在线粒体之外合成的前体蛋白。在本研究中，我们分析了外周苯二氮䓬受体（PBR）的拓扑形成，该受体通过五个疏水跨膜区段（TMS）整合到线粒体外膜（MOM）中，并在胆固醇向内膜的转运中发挥作用。对导入缺乏TOM组分的线粒体的体外和体内分析表明，PBR的导入：（1）依赖于导入受体Tom70，但既不需要Tom20和Tom22导入受体，也不需要导入通道Tom40；（2）与C端锚定蛋白共享Tom70之后的途径；（3）需要线粒体膜间隙的因子。此外，分别具有两个和四个TMS的线粒体外膜蛋白Mitofusins和线粒体泛素连接酶的膜整合，也通过相同的初始途径进行。这些发现揭示了一种以前未被识别的、具有多个TMS的线粒体外膜蛋白的膜整合途径。
