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Parkinson’s Disease
Volume 2011, Article ID 153979, 9 pages
http://dx.doi.org/10.4061/2011/153979
Research Article

PINK1-Interacting Proteins: Proteomic Analysis of Overexpressed PINK1

Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Maria-Goeppert-Straße 1, 23562 Lübeck, Germany

Received 22 November 2010; Accepted 22 December 2010

Academic Editor: Charleen T. Chu

Copyright © 2011 Aleksandar Rakovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Recent publications suggest that the Parkinson's disease- (PD-) related PINK1/Parkin pathway promotes elimination of dysfunctional mitochondria by autophagy. We used tandem affinity purification (TAP), SDS-PAGE, and mass spectrometry as a first step towards identification of possible substrates for PINK1. The cellular abundance of selected identified interactors was investigated by Western blotting. Furthermore, one candidate gene was sequenced in 46 patients with atypical PD. In addition to two known binding partners (HSP90, CDC37), 12 proteins were identified using the TAP assay; four of which are mitochondrially localized (GRP75, HSP60, LRPPRC, and TUFM). Western blot analysis showed no differences in cellular abundance of these proteins comparing PINK1 mutant and control fibroblasts. When sequencing LRPPRC, four exonic synonymous changes and 20 polymorphisms in noncoding regions were detected. Our study provides a list of putative PINK1 binding partners, confirming previously described interactions, but also introducing novel mitochondrial proteins as potential components of the PINK1/Parkin mitophagy pathway.