表没食子儿茶素没食子酸酯（EGCG）干扰CypD-p53互作调控线粒体通透性的分子机制

多酚类化合物在缓解细胞氧化损伤方面具有显著的效果，而线粒体通透性转换是细胞损伤过程中的核心事件。研究表明，线粒体亲环素D（CypD）是唯一在基因上确定的调节线粒体通透性转换孔（mPTP）开放的分子，而CypD-p53蛋白互作直接触发了氧化压力下mPTP的开启和导致细胞死亡。我们前期研究发现，表没食子儿茶素没食子酸酯（EGCG）能够与p53蛋白结合并引起p53的构象转变。因此，申请人提出EGCG通过直接干扰CypD-p53互作调控线粒体通透性的假说。本项目拟采用表面等离子共振、核磁共振和细胞学等手段从CypD-p53互作机理、EGCG干扰CypD-p53互作的方式和EGCG调控线粒体通透性表征三个方面展开研究，探索EGCG通过直接参与关键蛋白质互作来影响mPTP开放的机制，在分子-细胞层面深入揭示EGCG缓解细胞和线粒体损伤的机理，为多酚作为植物源功能基料在营养干预方面的应用提供理论支撑。

Polyphenols have been reported to be effective in alleviating the cell injury under oxidative stress. The mitochondrial permeability transition is a key event initiating cell death. To now, cyclophilin D (CypD) is the only genetically confirmed component involved in mitochondrial permeability transition pore (mPTP) formation and activity. The CypD-p53 interaction triggers the mPTP opening and cell death under oxidative stress. In our previous study, we found that epigallocatechin-3-gallate (EGCG) binds p53 and induces conformational changes in p53. Based on this, we propose that EGCG may inhibit the mPTP opening by interrupting the CypD-p53 interaction. Using SPR, NMR, MD simulation and cell assays, we will investigate the hypothesis in three parts: 1. The structural details in CypD-p53 interaction. 2. The molecular basis of EGCG interrupting CypD-p53 interaction. 3. The characterization of EGCG modulating mitochondrial permeability transition. We will explore how EGCG modulates mPTP opening through intervening protein-protein interaction, revealing the mechanism of the protective effect of EGCG on mitochondria, providing fundamental basis for the application of polyphenol in nutritional interventions.