继发性脊髓损伤是致残率极高、后果极其严重的脊柱外科疾病,但具体发病机制不明。申请者既往两项国家自然科学基金面上项目研究表明：促凋亡蛋白BAX线粒体特异性移位并诱发Drp1介导线粒体分裂，导致线粒体被特异性自噬降解是继发性脊髓损伤的重要分子机制。Drp1 VD结构域生物学功能丰富，因此我们推测此过程可能与Drp1 VD结构域密切相关(Cai WH:2012,IJN;2014 BR;2018 NRR;2019 JN)。本课题将在既往研究的基础之上，通过建立体外体内继发性脊髓损伤模型，采用WB、IP、IF、基因敲除、过表达等技术，探讨继发性脊髓损伤时Drp1 VD结构域多点磷酸化和泛素化修饰以及与Parkin蛋白RING2结构域相结合共定位于线粒体从而调节神经细胞线粒体分裂的具体机制。本课题将丰富继发性脊髓损伤时线粒体自噬与分裂的认识；在临床上，为早期治疗脊髓损伤提供坚实的理论基础。

Secondary spinal cord injury is an extremely disabling and serious spinal surgery disease, but the specific pathogenesis remians unknown. Our findings in two previous National Nature Science Foundation have proved that the pro-apopotic protein Bax specificity translocates to mitochrondria and induces Drp1-mediated mitochondrial division, thus leads to mitochondrial autophagy degradation is one of the important molecular mechanism in secondary spinal cord injury. Drp1 Variable domain has rich biological functions, so we speculate that this process may be closely related to Drp1 Variable domain (Cai WH: 2012, Int J Neurosci; 2014, Brain Res; 2018, Neural Regeneration Research; 2019, Journal of Neurotrauma). This project will be on the basis of previous studies and explore the multipoint phosphorylation and ubiquitin of Drp1 Varibale domain and the combination with Parkin protein RING2 domain in specific mechanisms of mitochondrial autophagy and divison by applying the secondary spinal cord injury model in vivo, in vitro, immunoblotting, immunoprecipitation, immunofluorescence, gene knock out and overexpression. This project will enrich the understanding of mitochondrial autophagy and division in secondary spinal cord injury. In clinical, it will provide a solid theoretical basis for early treatment of spinal cord injury.