Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76, Stockholm, Sweden.
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Sci Rep. 2017 Apr 13;7(1):880. doi: 10.1038/s41598-017-00853-x.
Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1 to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2 (MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in mammals. However, if and how these receptors work together in mitochondrial fission is poorly understood. Here we show that MIEFs interact with both Drp1 and Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex. Thus, MIEFs can regulate the interaction between Drp1 and Mff, and also Mff-induced Drp1 accumulation on mitochondria. It is shown that loss of endogenous MIEFs severely impairs these processes. Additionally, in cells depleted of endogenous MIEF1/2, high levels of exogenous MIEFs sequester Drp1 on the mitochondrial surface, resulting in mitochondrial elongation, whereas low-to-moderate levels of MIEFs promote mitochondrial fission, leading to mitochondrial fragmentation. In sum, the data suggest that MIEFs and Mff work coordinately in Drp1-mediated mitochondrial fission and that the level of MIEF1/2 relative to Mff sets the balance between mitochondrial fission and fusion.
线粒体动力学是一个基本的细胞过程，Drp1 向线粒体的募集是线粒体裂变的一个重要步骤。Mff 和 MIEF1/2（MiD51/49）作为哺乳动物中 Drp1 向线粒体募集的关键受体。然而，这些受体如何协同作用于线粒体裂变仍知之甚少。本文中，作者表示 MIEFs 在线粒体表面与 Drp1 和 Mff 相互作用，并作为衔接物将 Drp1 和 Mff 连接在一起，形成三聚体 Drp1-MIEF-Mff 复合物。因此，MIEFs 可以调节 Drp1 和 Mff 之间的相互作用，以及 Mff 诱导的 Drp1 在线粒体上的积累。研究表明，内源性 MIEFs 的缺失严重损害了这些过程。此外，在耗尽内源性 MIEF1/2 的细胞中，高水平的外源性 MIEFs 将 Drp1 隔离在线粒体表面，导致线粒体伸长，而低至中等水平的 MIEFs 则促进线粒体裂变，导致线粒体碎片化。总之，这些数据表明 MIEFs 和 Mff 在线粒体分裂中协同作用，MIEF1/2 相对于 Mff 的水平决定了线粒体裂变和融合之间的平衡。
