线粒体自噬在缺氧条件下适应机制的研究进展

由于线粒体能敏感地感受机体内氧浓度的变化,缺氧时会影响线粒体氧化磷酸化过程中电子传递链的正常功能,抑制ATP生成,产生大量活性氧(ROS)。ROS蓄积导致氧化损伤细胞内脂质、DNA和蛋白质等大分子物质,线粒体肿胀,通透性转换孔开放,释放细胞色素C等促凋亡因子,最终严重影响细胞的存活。因此这些功能异常或受损线粒体是缺氧应激状态下细胞是否存活的危险因素,及时清除这些线粒体,对维持线粒体质量、数量及细胞稳态具有重要意义。线粒体自噬是近年来发现的细胞适应缺氧的一种防御性代谢过程,它通过自噬途径选择性清除损伤、衰老和过量产生ROS的线粒体,促进线粒体更新和循环利用,确保细胞内线粒体功能稳定,保护缺氧应激下细胞的正常生长发挥重要的调节作用。本文就线粒体自噬在缺氧条件下发生过程、参与相关蛋白及调节机制等方面研究进行了综述。

The Progress of Study on Role of Mitophagy in Hypoxic Adaptation

Mitochondrial is sensitive effector which can feel the changes of oxygen concentration in cells. Hypoxia may influence the normal function of the electron transport chain during the process of mitochondrial oxidative phosphorylation, which lead to inhibit the production of ATP , generate a large amount of reactive oxygen species (ROS), result in oxidative damage of large molecules substances such as lipid, DNA and protein in cells, mitochondria swelling and permeability transition pore opening up, promoting the release of apoptosis factor such as cytochrome C, seriously threaten the survival of the cells in the end. So these dysfunction or damaged mitochondria are risk factors for cells survive or not under stress state. It is the great significance for the timely removal of these mitochondria to maintain the quality and quantity and steady homeostasis of mitochondrial. Mitophagy was recently found as a defensive metabolic response hypoxia. Mitophagy can selectively keep clear of overproduction of ROS and the aging and injury mitochondria, then promote the mitochondrial update and recycling, ensure the stability of mitochondrial function in cells, and ultimately promote cell survival under hypoxia. In this paper, we will overview the role, related proteins and regulating mechanism of mitophagy in adaptation to hypoxia.