期刊
MOLECULAR NEURODEGENERATION
卷 7, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1750-1326-7-40
关键词
Parkinson's disease; DJ 1; L166P; Mitochondria; Apoptosis; Bcl X-L; Bax; UVB
资金
- National High-tech Research and Development program of China 973-projects [2011CB504102]
- National Natural Sciences Foundation of China [30970921, 31100768]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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.
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