Unknown

Dataset Information

0

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


ABSTRACT:

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-XL 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-XL more strongly than wild-type DJ-1. In addition, UVB irradiation significantly promotes DJ-1(L166P) translocation to mitochondria and binding to Bcl-XL. DJ-1(L166P) but not wild-type DJ-1 dissociates Bax from Bcl-XL, 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-XL functions.

SUBMITTER: Ren H 

PROVIDER: S-EPMC3479024 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Ren Haigang H   Fu Kai K   Mu Chenchen C   Zhen Xuechu X   Wang Guanghui G  

Molecular neurodegeneration 20120814


<h4>Background</h4>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-XL and stabilizes it against ultraviolet B (UVB) irrad  ...[more]

Similar Datasets

| S-EPMC2118172 | biostudies-literature
| S-EPMC5348979 | biostudies-literature
| S-EPMC2422857 | biostudies-literature
| S-EPMC5635221 | biostudies-literature
| S-EPMC4849160 | biostudies-literature
| S-EPMC1900045 | biostudies-literature
| S-EPMC6099160 | biostudies-literature
| S-EPMC9695253 | biostudies-literature
| S-EPMC5870591 | biostudies-literature
| S-EPMC6888900 | biostudies-literature