Dynamic tubulation of mitochondria drives mitochondrial network formation.
Dynamic tubulation of mitochondria drives mitochondrial network formation.
复制标题
线粒体的动态管驱动线粒体网络形成。
DOI：
10.1038/cr.2015.89
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发表时间：
2015-10
期刊：
影响因子：
44.1
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Wang C;Du W;Su QP;Zhu M;Feng P;Li Y;Zhou Y;Mi N;Zhu Y;Jiang D;Zhang S;Zhang Z;Sun Y;Yu L
线粒体形成网络。线粒体网络的形成对于维持线粒体 DNA 完整性和交换线粒体材料非常重要，而线粒体网络的破坏会影响线粒体功能。根据目前的观点，线粒体网络是由单个线粒体融合形成的。在这里，我们报告了一种通过 KIF5B 介导的线粒体动态管形成线粒体网络的新机制。我们发现 KIF5B 将薄的、高度动态的小管从线粒体中拉出。这些动态小管的融合由线粒体融合蛋白介导，形成线粒体网络。我们通过使用纯化的具有融合能力的线粒体、重组 KIF5B 和聚合微管在体外重建线粒体网络，进一步证明动态管化和融合足以形成线粒体网络。有趣的是，KIF5B 仅控制细胞外围区域的网络形成，表明线粒体网络分为多个子区域，这些子区域可能通过不同的机制构建。我们的数据不仅揭示了线粒体网络形成的重要机制，而且还揭示了线粒体网络的不同部分是由不同的机制形成的。
Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.