双氢喋啶还原酶通过重塑蛋白质亚硝基化修饰促进线粒体自噬

线粒体自噬是一种选择性降解损伤线粒体的自噬形式，通常依赖泛素连接酶Parkin，但在Parkin缺陷的细胞中也能发生。然而，Parkin非依赖性线粒体自噬调控机制尚不完全清楚。我们发现参与调节蛋白质亚硝基化的二氢喋啶还原酶QDPR缺失阻滞Parkin非依赖性线粒体自噬。但蛋白质亚硝基化在Parkin非依赖性线粒体自噬中的作用不详。此外，上调蛋白质亚硝基化的外源NO供体可促进线粒体自噬，而调节Parkin非依赖性线粒体自噬的一些关键蛋白都可能发生亚硝基化修饰。因此，我们推断QDPR介导蛋白质亚硝基化极有可能在Parkin非依赖性线粒体自噬中也发挥重要作用。在本项目中，我们将以QDPR为切入点重点探究蛋白质亚硝基化在Parkin非依赖性线粒体自噬中的重要作用及机制。本项目将揭示QDPR通过重塑蛋白质亚硝基化调节Parkin非依赖性线粒体自噬，从而为明确蛋白质亚硝基化的生理病理意义提供理论基础。

As one kind of selective autophagy, mitophagy mediates the clearance of defective/superfluous mitochondria. While the E3 ligase Parkin is important to mitophagy, it can occur in cells without Parkin. However, the mechanisms of Parkin-independent mitophagy is still poorly understood. In the initial study for this proposal, we found that ablation of QDPR, which can regulate protein S-nitrosylation by producing S-nitron donor, blocked Parkin-independent mitophagy. While the relevance of protein S-nitrosylation is still not clear in Parkin-independent mitophagy，we also found that NO donor treatment in vitro accelerated mitophagy, and numerous key regulators might be S-nitrosylated in Parkin-independent mitophagy. Therefore, we proposed that protein S-nitrosylation mediated by QDPR has a high possibility to play a vital role in Parkin-independent mitophagy. In this study, we will take QDPR as a start point to explore how protein S-nitrosylation regulates Parkin-independent mitophagy process. By revealing the mechanism of QDPR to regulate Parkin-independent mitophagy via remodeling proteins S-nitrosylation, we believe that this study will provide a deep insight into the physiological and pathological relevance of protein S-nitrosylation.