Dataset Information

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

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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]

PMID: 22892098

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Dataset Information

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

Background

Results

Conclusion

Publications

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

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