Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany.
Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; Department of Neurology, University Medical Center, 37075 Göttingen, Germany.
Cell Metab. 2015 May 5;21(5):756-63. doi: 10.1016/j.cmet.2015.04.006.
The mitochondrial inner membrane is highly folded and displays a complex molecular architecture. Cristae junctions are highly curved tubular openings that separate cristae membrane invaginations from the surrounding boundary membrane. Despite their central role in many vital cellular processes like apoptosis, the details of cristae junction formation remain elusive. Here we identify Mic10, a core subunit of the recently discovered MICOS complex, as an inner mitochondrial membrane protein with the ability to change membrane morphology in vitro and in vivo. We show that Mic10 spans the inner membrane in a hairpin topology and that its ability to sculpt membranes depends on oligomerization through a glycine-rich motif. Oligomerization mutants fail to induce curvature in model membranes, and when expressed in yeast, mitochondria display an altered inner membrane architecture characterized by drastically decreased numbers of cristae junctions. Thus, we demonstrate that membrane sculpting by Mic10 is essential for cristae junction formation.
线粒体的内膜高度折叠，呈现出复杂的分子结构。嵴间腔是高度弯曲的管状开口，将嵴膜内陷与周围的界膜分隔开来。尽管嵴间腔在细胞凋亡等许多重要的细胞过程中起着核心作用，但嵴间腔形成的细节仍然难以捉摸。在这里，我们鉴定出 Mic10，这是最近发现的 MICOS 复合物的核心亚基，是一种具有在体外和体内改变膜形态能力的线粒体内膜蛋白。我们表明，Mic10 以发夹拓扑结构贯穿内膜，其形成膜的能力依赖于通过富含甘氨酸的基序进行寡聚化。寡聚化突变体不能在模型膜中诱导曲率，当在酵母中表达时，线粒体显示出改变的内膜结构，特征是嵴间腔数量急剧减少。因此，我们证明了 Mic10 通过塑造膜对于嵴间腔的形成是必不可少的。
