DJ-1 function and oxidative stress

DJ-1突变是一种非常罕见的导致隐性帕金森病的原因，在世界范围内占少数病例。几个实验室已经证明，尽管精确的分子功能尚不清楚，但所涉及的蛋白质与氧化应激反应有关。在细胞水平上，DJ-1缺失的影响之一是线粒体功能受损。这可能与氧化应激有关，因为线粒体是活性氧（ROS）的主要来源，尽管这一点尚不确定。在过去的几年里，我们已经确定了DJ-1蛋白中的一些关键残基，它们对细胞功能很重要，特别是半胱氨酸106，它在暴露于ROS和谷氨酸18后被修饰，它稳定了修饰的C106残基。

DJ-1 mutations are a very rare cause of recessive parkinsonism, accounting for a handful of cases worldwide. The protein involved has been shown by several laboratories to be involved in oxidative stress responses although the precise molecular function is unknown. At a cellular level, one of the effects of a loss of DJ-1 is that mitochondrial function is compromised. This may be related to oxidative stress, as mitchondria are a major source of reactive oxygen species (ROS), although this is uncertain. In prior years, we have identified some of the key residues in the DJ-1 protein that are important for cellular function, particularly cysteine 106 which becomes modified after exposure to ROS and glutamate 18, which stabilizes the modified C106 residue. To try and develop our ideas about DJ-1 further, we have been exploring two aspects of its function. First, we have started to characterize the effects of DJ-1 deficiency on mitochondrial function. We find that a lack of DJ-1 causes loss of mitochondrial membrane potential and an increase in markers of autophagy, the process by which defective mitochondria are removed from the cell. Second, we have developed novel mutations that identify functionally critical sites on DJ-1 for protection against mitochondrial damage.