Abstract
Background: Mutations or deletions in DJ-1/PARK7 gene are causative for recessive forms of early onset Parkinsons 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-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-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.
Original language | English (US) |
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Article number | 40 |
Journal | Molecular neurodegeneration |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - 2012 |
Externally published | Yes |
Keywords
- Apoptosis
- Bax
- Bcl-X
- DJ-1
- L166P
- Mitochondria
- Parkinsons disease
- UVB
ASJC Scopus subject areas
- Molecular Biology
- Clinical Neurology
- Cellular and Molecular Neuroscience