Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation.
Rare genetic mutations in the DJ-1 and Parkin genes cause recessive Parkinsonism, however, the relationship between these two genes is not fully elucidated. Current emerging evidence suggests that these genes are involved in mitochondrial homeostasis, and that a deficiency in either of these two genes is associated with damages in mitochondrial function and morphology. In this study, we demonstrated that knockdown of DJ-1 expression or the overexpression of the DJ-1 L166P mutation results in a damaged phenotype in mitochondria and a hypersensitivity to H2O2-induced cell apoptosis. These phenotypes result from increased levels of endogenous oxidative stress. However, overexpression of wild-type Parkin rescued the phenotypes observed in the mitochondria of DJ-1 knockdown and DJ-1 L166P mutant cells. We also determined that there were differences between the two cell models. Furthermore, both H₂O₂ treatment and the DJ-1 L166P mutation weakened the interaction between DJ-1 and Parkin. Taken together, these findings suggested that DJ-1 and Parkin were linked through oxidative stress, and that overexpression of Parkin protects DJ-1 protein-deficient and DJ-1 L166P mutant-expressing cells via inhibition of oxidative stress.
Department of Cellular and Genetic Medicine, School of Basic Medical Sciences Fudan University, Dong' an Road, BOX 239, Shanghai, 200032, People's Republic of China.
Chunyan
C
Chang
Guolu
G
Wu
Peiye
P
Gao
Ling
L
Yang
Wen
W
Liu
Ji
J
Zuo
D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D020125:Mutation, Missense; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1