脊髓损伤后神经元会出现自噬和自噬蛋白LC3、Beclin1表达增高已有报道，我们首次发现了脊髓损伤线粒体自噬（mitophagy）和细胞死亡蛋白BNIP3、p53表达增高。BNIP3由缺氧诱导因子-1α诱导和p53负性调控表达，通过与Bcl2-Beclin1竞争结合介导自噬引起细胞死亡。但脊髓损伤后p53如何转录后调控BNIP3表达、BNIP3如何介导的线粒体自噬信号通路还不清楚。因此，我们猜想脊髓损伤后p53与自身mRNA结合转录后调控BNIP3表达，线粒体膜结合的BNIP3与自噬体膜复合结构体上的LC3相互作用，将线粒体包裹在自噬体膜内而发生线粒体自噬。为此，本研究将观测p53与自身mRNA结合转录后调控BNIP3表达、线粒体-BNIP3-LC3-自噬体膜复合结构体的形成、抑制BNIP3后对脊髓损伤后神经元的保护。本研究为线粒体自噬确定新的信号通路，为脊髓损伤神经元提供潜在的保护方式。

In spinal cord injury (SCI), autophagy and autophagic associated protein LC3 and Beclin-1 expression was reported. Our preliminary data indicated mitophagy in electron microscopy and cell death protein BNIP3 and p53 expression after SCI. BNIP3 is transcriptionally upregulated by hypoxia inducible factor-1 and downregulated by p53, and causes mitochondrial permeabilization and dysfunction leading to cell autophagy , which compete with Beclin 1-Bcl-2 complexes followed by releasing Beclin-1 from the complex and then enhancing autophagy. However, the mechanisms of p53 postranscriptinal regulation of BNIP3 and signal transduction of BNIP3 induced mitophagy are not clear. We hypothesize that p53 protein, bound to its own mRNA, inhibits the autologous translation reaction which downregulate BNIP3 expression in neuron; BNIP3, targeted to mitochondria, interact with LC3, which targeted to autophagosome, and form mitochondria-BNIP3-LC3-autophagosome complex， which leading to mitophagy. In this study, we will investigate the mechanism by which p53 protein bound to its own mRNA to downregulate BNIP3 expression in neuron; demonstrate if Bnip3 also interacts with LC3 to induce mitophagy after SCI; and evaluate protective neuronal effects of BNIP3 inhibition after SCI. Hopefully, this study will demonstrate a new mitophagy signal transduction pathway and provide a potential neuron protection way after SCI

脊髓损伤后神经元会出现自噬和自噬蛋白LC3、Beclin1表达增高已有报道，我们首次发现了脊髓损伤线粒体自噬（mitophagy）和细胞死亡蛋白BNIP3、p53表达增高。BNIP3由缺氧诱导因子-1α诱导和p53负性调控表达，通过与Bcl2-Beclin1竞争结合介导自噬引起细胞死亡。但脊髓损伤后p53如何转录后调控BNIP3表达、BNIP3如何介导的线粒体自噬信号通路还不清楚。因此，本课题将检测缺氧神经元的超微结构以及线粒体自噬相关蛋白在线粒体中的表达变化；检测BNIP3、NIX与LC3的相互作用以及线粒体-BNIP3-LC3-自噬体膜复合结构体的形成；抑制BNIP3、NIX对线粒体自噬的影响以及缺氧脊髓神经元的作用。我们通过透射电镜、免疫荧光、WB、免疫共沉淀、线粒体功能检测等方法发现：大鼠脊髓神经元缺氧后神经元线粒体自噬被诱导激活；线粒体自噬相关蛋白BNIP3诱导缺氧神经元线粒体自噬；通过RNA干扰抑制BNIP3的表达保护了缺氧引起的神经元死亡。本研究为线粒体自噬确定新的信号通路，为脊髓损伤神经元提供潜在的保护方式。