Li Hong Mei, Niki Takeshi, Taira Takahiro, Iguchi-Ariga Sanae M M, Ariga Hiroyoshi
Graduate School of Agriculture, Hokkaido University, Sapporo, 060-8589, Japan.
Free Radic Res. 2005 Oct;39(10):1091-9. doi: 10.1080/10715760500260348.
DJ-1 is a novel oncogene and causative gene for familial form of the Parkinson's disease (PD). DJ-1 has been shown to play a role in anti-oxidative stress by eliminating reactive oxygen species (ROS). The onset of PD is thought to be caused by oxidative stress and mitochondrial injury, which leads to protein aggregation that results in neuronal cell death. However, the mechanism by which DJ-1 triggers the onset of PD is still not clear. In this study, we analyzed association and localization of DJ-1 and its mutants with various chaperones. The results showed that DJ-1 and its mutants were associated with Hsp70, CHIP and mtHsp70/Grp75, a mitochondria-resident Hsp70, and that L166P and M26I mutants found in PD patients were strongly associated with Hsp70 and CHIP compared to wild-type and other DJ-1 mutants. DJ-1 and its mutants were colocalized with Hsp70 and CHIP in cells. Furthermore, association and colocalization of wildtype DJ-1 with mtHsp70 in mitochondria were found to be enhanced by treatment of cells with H2O2. These results suggest that translocation of DJ-1 to mitochondria after oxidative stress is carried out in association with chaperones.
DJ-1是一种新型癌基因，也是家族性帕金森病（PD）的致病基因。研究表明，DJ-1通过清除活性氧（ROS）在抗氧化应激中发挥作用。PD的发病被认为是由氧化应激和线粒体损伤引起的，这会导致蛋白质聚集，进而导致神经元细胞死亡。然而，DJ-1引发PD发病的机制仍不清楚。在本研究中，我们分析了DJ-1及其突变体与各种分子伴侣的关联和定位。结果表明，DJ-1及其突变体与Hsp70、CHIP以及线粒体驻留Hsp70即mtHsp70/Grp75相关联，并且与野生型和其他DJ-1突变体相比，在PD患者中发现的L166P和M26I突变体与Hsp70和CHIP的关联更强。DJ-1及其突变体在细胞中与Hsp70和CHIP共定位。此外，用H2O2处理细胞后，发现野生型DJ-1与线粒体中mtHsp70的关联和共定位增强。这些结果表明，氧化应激后DJ-1与分子伴侣协同作用转运至线粒体。
