Mitochondrial localization of DJ-1 leads to enhanced neuroprotection.

Journal of Neuroscience Research
Eunsung JunnM Maral Mouradian

Abstract

Mutations in DJ-1 (PARK7) cause recessively inherited Parkinson's disease. DJ-1 is a multifunctional protein with antioxidant and transcription modulatory activity. Its localization in cytoplasm, mitochondria, and nucleus is recognized, but the relevance of this subcellular compartmentalization to its cytoprotective activity is not fully understood. Here we report that under basal conditions DJ-1 is present mostly in the cytoplasm and to a lesser extent in mitochondria and nucleus of dopaminergic neuroblastoma SK-N-BE(2)C cells. Upon oxidant challenge, more DJ-1 translocates to mitochondria within 3 hr and subsequently to the nucleus by 12 hr. The predominant DJ-1 species in both mitochondria and nucleus is a dimer believed to be the functional form. Mutating cysteine 106, 53, or 46 had no impact on the translocation of DJ-1 to mitochondria. To study the relative neuroprotective activity of DJ-1 in mitochondria and nucleus, DJ-1 cDNA constructs fused to the appropriate localization signal were transfected into cells. Compared with 30% protection against oxidant-induced cell death in wild-type DJ-1-transfected cells, mitochondrial targeting of DJ-1 provided a significantly stronger (55%) cytoprotection based on lactate dehydroge...Continue Reading

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Citations

Nov 12, 2009·Journal of Bioenergetics and Biomembranes·Sergio PapaClaudia Piccoli
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Jul 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Eunsung JunnM Maral Mouradian
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Apr 14, 2010·Neuroscience Research·Joo-Young ImM Maral Mouradian

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