Sumol conjugates and participates in mitochondrial substrates mitochondrial fission
Sumol conjugates and participates in mitochondrial substrates mitochondrial fission
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DOI：
10.1016/j.cub.2004.02.004
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发表时间：
2004-02-17
期刊：
影响因子：
9.2
通讯作者：
McBride, H
中科院分区：
文献类型：
--
作者：
Harder, Z;Zunino, R;McBride, H
线粒体分裂需要进化上保守的动力相关蛋白 (DRP1)，该蛋白从胞质溶胶募集到线粒体外膜以协调膜分裂 [1]。目前，DRP1 在线粒体上的募集和组装机制尚不清楚。在这里，我们将 Ubc9 和 Sumo1 鉴定为特定的 DRP1 相互作用蛋白，并证明 DRP1 是 Sumo1 底物。此外，在线粒体组分中观察到数量惊人的 Sumo1 缀合物，表明 sumo 化是一种常见的线粒体修饰。视频显微镜显示 YFP:Sumo1 经常在线粒体裂变部位发现，并且与碎片化线粒体的尖端保持紧密联系。与此一致的是，荧光显微镜显示总胞质 YFP:Sumo1 的一部分与内源性线粒体 DRP1 共定位。最后，Sumo1 的瞬时转染显着提高了线粒体断裂的水平。对内源性 DRP1 水平的分析表明，Sumo1 的过度表达可以特异性地保护 DRP1 免遭降解，从而产生更稳定、更活跃的 DRP1 库，这至少部分解释了过度片段化。总之，这些数据首次确定了 Sumo1 在线粒体上的功能，并表明 Sumo1 在线粒体裂变中的参与具有新的作用。
Mitochondrial fission requires the evolutionarily conserved dynamin related protein (DRP1), which is recruited from the cytosol to the mitochondrial outer membrane to coordinate membrane scission [1]. Currently, the mechanism of recruitment and assembly of DRP1 on the mitochondria is unclear. Here, we identify Ubc9 and Sumo1 as specific DRP1-interacting proteins and demonstrate that DRP1 is a Sumo1 substrate. In addition, a surprising number of Sumo1 conjugates were observed in the mitochondrial fractions, suggesting that sumoylation is a common mitochondrial modification. Video microscopy demonstrates that YFP:Sumo1 is often found at the site of mitochondrial fission and remains tightly associated to the tips of fragmented mitochondria. Consistent with this, fluorescence microscopy revealed that a portion of total cytosolic YFP:Sumo1 colocalizes with endogenous mitochondrial DRP1. Finally, transient transfection of Sumo1 dramatically increases the level of mitochondrial fragmentation. Analysis of endogenous DRP1 levels indicates that overexpression of Sumo1 specifically protects DRP1 from degradation, resulting in a more stable, active pool of DRP1, which at least partially accounts for the excess fragmentation. Together, these data are the first to identify a function for Sumo1 on the mitochondria and suggest a novel role for the participation of Sumo1 in mitochondrial fission.