Nek9磷酸化MCL-1调控线粒体自噬和分裂的机制与功能研究

线粒体是细胞中重要的细胞器，其处于分裂和融合的动态平衡网络中，并受到非常复杂的调控。在细胞有丝分裂时期线粒体的分裂和融合受到了严格的调控，除了染色质被平均分配到子代细胞中，线粒体也会被分配到子代细胞中。Nek9是细胞有丝分裂时期重要的激酶，除了在细胞有丝分裂时期调控纺锤体的结构与功能，是否在细胞器特别是线粒体的分裂分配中起到关键作用，有丝分裂时期线粒体的分裂是否还有其他重要蛋白参与，是急需回答的问题。本研究的前期工作鉴定到MCL-1作为一个新的线粒体自噬受体蛋白参与线粒体分裂的调控，并发现Nek9激酶可以磷酸化MCL-1。本项目在前期研究的基础上，拟通过生化细胞生物学手段进一步确证Nek9对MCL-1磷酸化的调控，揭示Nek9通过磷酸化MCL-1调控线粒体分裂和线粒体自噬的机制，并系统揭示Nek9磷酸化MCL-1在细胞有丝分裂过程中介导线粒体分裂的生理功能。

Mitochondria are important organelles in cells, which are in a dynamic equilibrium network of fusion and fission and are subject to very complex regulation. Mitochondrial fission and fusion are tightly regulated during cell mitosis. Nek9 is an important kinase during mitosis. In addition to regulating the structure and function of spindles, more studies are needed to answer the regulation of Nek9 on organelles, especially mitochondria during mitosis. Previous work in this study identified MCL-1 as a novel mitophagy receptor protein involved in the regulation of mitochondrial fission and found that Nek9 kinase can phosphorylate MCL-1. On the basis of previous studies, this project intends to further confirm the regulation of Nek9 on MCL-1 phosphorylation by using biochemical and cell biological technology, reveal the mechanism of Nek9 regulating mitochondrial fission and mitophagy by phosphorylating MCL-1, and systematically reveal the physiological function of Nek9 phosphorylating MCL-1 in mediating mitochondrial fission during cell mitosis.