L166P mutant DJ-1 promotes cell death by dissociating Bax from mitochondrial Bcl-XL

Molecular Neurodegeneration

Guanghui Wang¹  Xuechu Zhen¹  Chenchen Mu¹  Kai Fu¹  Haigang Ren¹ 

[1] Department of Pharmacology, Laboratory of Molecular Neuropathology, Soochow University College of Pharmaceutical Sciences, Suzhou, Jiangsu, 215123, People’s Republic of China

关键词: UVB;    Bax;    Bcl-X_L;    Apoptosis;    Mitochondria;    L166P;    DJ-1;    Parkinson’s disease;   

Others  :  863781
DOI  :  10.1186/1750-1326-7-40

 received in 2012-03-25, accepted in 2012-08-06,  发布年份 2012

【 摘 要 】

Background

Mutations or deletions in DJ-1/PARK7 gene are causative for recessive forms of early onset Parkinson’s disease (PD). Wild-type DJ-1 has cytoprotective roles against cell death through multiple pathways. The most commonly studied mutant DJ-1(L166P) shifts its subcellular distribution to mitochondria and renders cells more susceptible to cell death under stress stimuli. We previously reported that wild-type DJ-1 binds to Bcl-X_L and stabilizes it against ultraviolet B (UVB) irradiation-induced rapid degradation. However, the mechanisms by which mitochondrial DJ-1(L166P) promotes cell death under death stimuli are largely unknown.

Results

We show that DJ-1(L166P) is more prone to localize in mitochondria and it binds to Bcl-X_L more strongly than wild-type DJ-1. In addition, UVB irradiation significantly promotes DJ-1(L166P) translocation to mitochondria and binding to Bcl-X_L. DJ-1(L166P) but not wild-type DJ-1 dissociates Bax from Bcl-X_L, thereby leading to Bax enrichment at outer mitochondrial membrane and promoting mitochondrial apoptosis pathway in response to UVB irradiation.

Conclusion

Our findings suggest that wild-type DJ-1 protects cells and DJ-1(L166P) impairs cells by differentially regulating mitochondrial Bax/Bcl-X_L functions.

【 授权许可】

   
2012 Ren et al.; licensee BioMed Central Ltd.

【 图 表 】

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