Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress.
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.
Li
Hong Mei
HM
Graduate School of Agriculture, Hokkaido University, Sapporo, 060-8589, Japan.
Niki
Takeshi
T
Taira
Takahiro
T
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D000818:Animals; D002460:Cell Line; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000187:drug effects
D018840:HSP70 Heat-Shock Proteins; D007976:Leupeptins; D015513:Oncogene Proteins; D061988:Proteasome Inhibitors; D006861:Hydrogen Peroxide; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde