Midbody ring disposal by autophagy is a post-abscission event of cytokinesis
Midbody ring disposal by autophagy is a post-abscission event of cytokinesis
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DOI：
10.1038/ncb1813
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发表时间：
2009-01-01
影响因子：
21.3
通讯作者：
Jentsch, Stefan
中科院分区：
文献类型：
--
作者：
Pohl, Christian;Jentsch, Stefan
在细胞质分裂结束时，分裂的细胞通过细胞间桥连接在一起，其中包括中体和一个被称为中体环的单一的、密集泛素化的圆形结构（Mr）（1-3）。最近的研究表明Mr可以作为膜传递的靶点和未来子细胞之间的物理屏障（2,3）。Mr在末期物化，在细胞质分裂期间定位于细胞间桥，并在脱落后不对称地移动到一个细胞中（2,3）。子细胞很少积累以前分裂的MRs(2,3)，但这些大结构最终如何消失仍然未知。在这里，我们发现MRs通过自噬被丢弃，这包括它们被隔离到自噬体中并被递送到溶酶体中进行降解。值得注意的是，自噬因子，如泛素受体p62（参考文献4,5）和泛素相关蛋白Atg8（参考文献6），在脱落过程中与Mr相关，表明自噬与细胞分裂相耦合。此外，Mr在溶酶体储存障碍患者的细胞中积累，表明Mr处置缺陷是这些疾病的特征。因此，我们的研究结果表明，自噬具有比以前认为的更广泛的作用，并且通过清除多余的大分子组装（如MRs）来进行细胞修复是一种重要的自噬功能。
At the end of cytokinesis, the dividing cells are connected by an intercellular bridge, containing the midbody along with a single, densely ubiquitylated, circular structure called the midbody ring (Mr)(1-3). recent studies revealed that the Mr serves as a target site for membrane delivery and as a physical barrier between the prospective daughter cells(2,3). the Mr materializes in telophase, localizes to the intercellular bridge during cytokinesis, and moves asymmetrically into one cell after abscission(2,3). Daughter cells rarely accumulate MRs of previous divisions(2,3), but how these large structures finally disappear remains unknown. Here, we show that MRs are discarded by autophagy, which involves their sequestration into autophagosomes and delivery to lysosomes for degradation. Notably, autophagy factors, such as the ubiquitin adaptor p62 (refs 4, 5) and the ubiquitin-related protein Atg8 (ref. 6), associate with the Mr during abscission, suggesting that autophagy is coupled to cytokinesis. Moreover, MRs accumulate in cells of patients with lysosomal storage disorders, indicating that defective Mr disposal is characteristic of these diseases. thus our findings suggest that autophagy has a broader role than previously assumed, and that cell renovation by clearing from superfluous large macromolecular assemblies, such as MRs, is an important autophagic function.