适度的线粒体自噬可以清除损伤线粒体，但过度线粒体自噬是否对线粒体造成损伤则少有研究。PINK1/Parkin途径是线粒体自噬的重要途径。本项目前期证明：1.抑制线粒体自噬及PINK1表达可改善脂多糖（LPS）介导的肺泡II型上皮细胞（AECII）线粒体损伤，提示脓毒症急性肺损伤（SIALI）中过度线粒体自噬导致线粒体损伤；2.LPS通过TNF-α介导PINK1/Parkin线粒体自噬；3.抑制Bad表达可减少Parkin转位至线粒体，提示Bcl-2家族蛋白参与PINK1/Parkin线粒体自噬；4.LPS介导细胞坏死性凋亡。本课题将利用分子和细胞生物学方法，在细胞及整体水平查明LPS是否可通过TNF-α和Bcl-2家族蛋白，分别上调PINK1表达，促进Parkin转位，介导过度线粒体自噬，导致AECII线粒体损伤和坏死性凋亡，探讨PINK1/Parkin线粒体自噬在SIALI的作用及机制。

Studies have demonstrated that injuried mitochondria can be removed via mild mitophagy, however, it's unclear that whether the hypernomic mitophagy promotes mitochondria injury. The PINK1/Parkin pathway is important for mitophagy. Based on our previously studies, we found that: 1. suppression of PINK1 and mitophagy could attenuate lipopolysaccharide (LPS)-induced mitochondria injury in type II alveolar epithelial cells (AEC II), which indicated that hypernomic mitophagy result in mitochondria injury in sepsis-induced acute lung injury (SIALI); 2. LPS induced PINK1/Parkin dependent mitophagy via TNF-α; 3. supression of Bad could inhibits the translocation of Parkin to mitochondria; 4. LPS could induce AEC II necroptosis. According to these results, with molecular biological techniques, our study mainly focus on discussing that whether LPS could up-regulates PINK1 and promotes Parkin transposition respectively by TNF-α and Bcl-2 family proteins, to induce AEC II's mitochondria injury and necroptosis. In this study, we will investigate the effects and mechanism of PINK1/Parkin dependent mitophagy in SIALI.