Liu Xingguo, Weaver David, Shirihai Orian, Hajnóczky György
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
EMBO J. 2009 Oct 21;28(20):3074-89. doi: 10.1038/emboj.2009.255. Epub 2009 Sep 10.
Visualizing mitochondrial fusion in real time, we identified two classes of fusion events in mammalian cells. In addition to complete fusion, we observed transient fusion events, wherein two mitochondria came into close apposition, exchanged soluble inter-membrane space and matrix proteins, and re-separated, preserving the original morphology. Transient fusion exhibited rapid kinetics of the sequential and separable mergers of the outer and inner membranes, but allowed only partial exchange of integral membrane proteins. When the inner membrane fusion protein Opa1 level was lowered or was greatly elevated, transient fusions could occur, whereas complete fusions disappeared. Furthermore, transient fusions began from oblique or lateral interactions of mitochondria associated with separate microtubules, whereas complete fusions resulted from longitudinal merging of organelles travelling along a single microtubule. In contrast to complete fusion, transient fusions both required and promoted mitochondrial motility. Transient fusions were also necessary and sufficient to support mitochondrial metabolism. Thus, Opa1 expression and cytoskeletal anchorage govern a novel form of fusion that has a distinct function in mitochondrial maintenance.
通过实时观察线粒体融合过程，我们在哺乳动物细胞中鉴定出两类融合事件。除了完全融合外，我们还观察到瞬时融合事件，即两个线粒体紧密靠近，交换可溶性膜间隙和基质蛋白，然后重新分离，保持原始形态。瞬时融合表现出内膜和外膜顺序且可分离融合的快速动力学，但仅允许整合膜蛋白部分交换。当内膜融合蛋白Opa1水平降低或大幅升高时，会发生瞬时融合，而完全融合则消失。此外，瞬时融合始于与单独微管相关的线粒体的倾斜或侧向相互作用，而完全融合则是由沿着单个微管移动的细胞器纵向合并导致的。与完全融合不同，瞬时融合既需要线粒体运动性，也会促进线粒体运动性。瞬时融合对于维持线粒体代谢也是必要且充分的。因此，Opa1的表达和细胞骨架锚定作用控制着一种新型融合形式，这种融合形式在维持线粒体功能方面具有独特作用。
