Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions.
Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions.
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DOI：
10.1038/ncomms15258
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发表时间：
2017-05-31
影响因子：
16.6
通讯作者：
Daumke O
中科院分区：
文献类型：
--
作者：
Hessenberger M;Zerbes RM;Rampelt H;Kunz S;Xavier AH;Purfürst B;Lilie H;Pfanner N;van der Laan M;Daumke O
线粒体接触位点和嵴组织系统（MICOS）对于嵴连接和线粒体内膜结构的形成至关重要。 MICOS 包含两个核心组件。 Mic10 显示膜弯曲活性，而 Mic60（丝裂素）形成内膜和外膜之间的接触位点。在此，我们报道 Mic60 使脂质体变形为薄膜小管，从而表现出膜成形活性。我们在 Mic60 的可溶性膜间空间暴露部分中确定了一个膜结合位点。该膜结合位点是由保守的卷曲螺旋和丝裂蛋白结构域之间预计的两亲性螺旋形成的。 Mitofilin 结构域负向调节 Mic60 的膜成形活性。 Mic19 与 mitofilin 结构域的结合可调节该活性。保守的 Mic60-Mic19 复合物的膜结合和成形对于嵴连接形成、线粒体膜结构和有效的呼吸活动至关重要。因此，Mic60 通过塑造内膜嵴连接和形成与外膜的接触位点发挥双重作用。 MICOS 复合体在嵴连接形成和线粒体内膜形态中具有重要作用。在这里，作者表明，其成分之一 Mic60 已知可形成内膜和外膜之间的接触位点，也显示出膜成形活性。
The mitochondrial contact site and cristae organizing system (MICOS) is crucial for the formation of crista junctions and mitochondrial inner membrane architecture. MICOS contains two core components. Mic10 shows membrane-bending activity, whereas Mic60 (mitofilin) forms contact sites between inner and outer membranes. Here we report that Mic60 deforms liposomes into thin membrane tubules and thus displays membrane-shaping activity. We identify a membrane-binding site in the soluble intermembrane space-exposed part of Mic60. This membrane-binding site is formed by a predicted amphipathic helix between the conserved coiled-coil and mitofilin domains. The mitofilin domain negatively regulates the membrane-shaping activity of Mic60. Binding of Mic19 to the mitofilin domain modulates this activity. Membrane binding and shaping by the conserved Mic60–Mic19 complex is crucial for crista junction formation, mitochondrial membrane architecture and efficient respiratory activity. Mic60 thus plays a dual role by shaping inner membrane crista junctions and forming contact sites with the outer membrane. The MICOS complex has an essential role in crista junction formation and mitochondrial inner membrane morphology. Here, the authors show that one of its components, Mic60, known to form contact sites between inner and outer membranes, also displays membrane-shaping activity.