团头鲂Bcl2l13在低氧介导线粒体自噬和细胞凋亡中的调节机制

线粒体是低氧损害的靶细胞器，受损的线粒体通过自噬清除，是细胞适应低氧的重要途经，因此解析线粒体自噬调节机制成为研究低氧适应的重要内容。前期研究我们发现低氧可导致团头鲂线粒体功能异常及细胞凋亡，Bcl2l13（Bcl2-like 13）基因表达上调。然而Bcl2l13作为酵母ATG32的同源蛋白其在线粒体自噬中的作用机制还不清楚，同时Bcl2l13具有促凋亡和抗凋亡双重功能，那么该基因如何实现其功能转换？在鱼类细胞凋亡中的作用是什么？为了进一步研究Bcl2l13在鱼类低氧介导的线粒体自噬和细胞凋亡中的功能，本项目拟基于启动子活性分析、酵母双杂交等研究低氧介导的团头鲂Bcl2l13的上下游调控因子，通过基因抑制、结构域缺失等实验在分子、细胞及机体水平分析该基因在线粒体自噬和细胞凋亡中的作用机制。本研究结果将为鱼类低氧适应的调节机制研究注入新内容。

Mitochondrion is the target of hypoxia damage, and damaged mitochondria are removed by mitophagy, which is an important pathway of hypoxia adaptation, therefore, understanding regulatory mechanisms of mitophagy becomes an important part to study hypoxia adaptation. Our previous study found that hypoxia could result in mitochondrial dysfunction and cell apoptosis of Megalobrama amblycephala, and up-regulated expression of bcl2l13 (Bcl2-like 13). However, as the homologous protein of yeast ATG32, Bcl2l13 function in mitophagy is unclear in mitophagy. Additionally, Bcl2l13 has double functions with promoting or inhibiting apoptosis, but it is unknown about Bcl2l13 roles in fish apoptosis. Therefore, in the present study, in order to further study Bcl2l13 functions in fish mitophagy and apoptosis regulated by hypoxia, upstream and downstream regulatory factors of M. amblycephala Bcl2l13 will be confirmed based on promotor activity analysis and yeast two hybridization etc. Functions of the gene in mitophagy and apoptosis will be studied based on gene inhibition and motif deletion at molecular, cellular and individual levels. Our results will contribute to systematically understand molecular regulatory mechanisms of fish hypoxia adaptation.