PINK1 controls mitochondrial localization of Parkin through direct phosphorylation

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PTEN-induced putative kinase 1 (PINK 1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function. However, the mechanism of their interaction at the biochemical level has not been investigated yet. Using both mammalian and Drosophila systems, we here demonstrate that the PINK1 kinase activity is required for its function in mitochondria, PINK1 regulates the localization of Parkin to the mitochondria in its kinase activity-dependent manner. In detail, Parkin phosphorylation by PINK1 on its linker region promotes its mitochondrial translocation, and the RING1 domain of Parkin is critical for this Occurrence. These results demonstrate the biochemical relationship between PINK1, Parkin, and the mitochondria and thereby suggest the possible mechanism of PINK-Parkin-associated PD pathogenesis. (C) 2008 Elsevier Inc. All rights reserved.
Publisher
Academic Press Inc Elsevier Science
Issue Date
2008-12
Language
English
Article Type
Article
Keywords

RECESSIVE PARKINSONISM; MUTATIONS; DROSOPHILA-PINK1; PATHOLOGY; KINASE-1; MUTANTS; DISEASE; RING

Citation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.377, no.3, pp.975 - 980

ISSN
0006-291X
DOI
10.1016/j.bbrc.2008.10.104
URI
http://hdl.handle.net/10203/89889
Appears in Collection
BS-Journal Papers(저널논문)
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