Oxidized DJ-1 interacts with the mitochondrial protein BCL-X L

Haigang Ren, Kai Fu, Dan Wang, Chenchen Mu, Guanghui Wang

Research output: Contribution to journalArticle

Abstract

Parkinson disease (PD)- and cancer-associated protein, DJ-1, mediates cellular protection via many signaling pathways. Deletions or mutations in the DJ-1 gene are directly linked to autosomal recessive early-onset PD. DJ-1 has potential roles in mitochondria. Here, we show that DJ-1 increases its mitochondrial distribution in response to ultraviolet B (UVB) irradiation and binds to Bcl-X L. The interactions between DJ-1 and Bcl-X L are oxidation-dependent. DJ-1(C106A), a mutant form of DJ-1 that is unable to be oxidized, binds Bcl-X L much less than DJ-1 does. Moreover, DJ-1 stabilizes Bcl-X L protein level by inhibiting its ubiquitination and degradation through ubiquitin proteasome system (UPS) in response to UVB irradiation. Furthermore, under UVB irradiation, knockdown of DJ-1 leads to increases of Bcl-X L ubiquitination and degradation upon UVB irradiation, thereby increasing mitochondrial Bax, caspase-3 activation and PARP cleavage. These data suggest that DJ-1 protects cells against UVB-induced cell death dependent on its oxidation and its association with mitochondrial Bcl-X L.

Original languageEnglish (US)
Pages (from-to)35308-35317
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number40
DOIs
StatePublished - Oct 7 2011
Externally publishedYes

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Ubiquitination
Mitochondrial Proteins
bcl-X Protein
Irradiation
Sequence Deletion
Parkinsonian Disorders
Proteasome Endopeptidase Complex
Ubiquitin
Caspase 3
Mitochondria
Cell Death
Degradation
Oxidation
Cell death
Genes
Neoplasms
Chemical activation
Association reactions
Proteins
Parkinson Disease Associated Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oxidized DJ-1 interacts with the mitochondrial protein BCL-X L . / Ren, Haigang; Fu, Kai; Wang, Dan; Mu, Chenchen; Wang, Guanghui.

In: Journal of Biological Chemistry, Vol. 286, No. 40, 07.10.2011, p. 35308-35317.

Research output: Contribution to journalArticle

Ren, Haigang ; Fu, Kai ; Wang, Dan ; Mu, Chenchen ; Wang, Guanghui. / Oxidized DJ-1 interacts with the mitochondrial protein BCL-X L In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 40. pp. 35308-35317.
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