Compelling evidence indicates that two autosomal recessive Parkinson's disease genes, PINK1 (PARK6) and Parkin (PARK2), cooperate to mediate the autophagic clearance of damaged mitochondria (mitophagy). Mutations in the F-box domain-containing protein Fbxo7 (encoded by PARK15) also cause early-onset autosomal recessive Parkinson's disease, by an unknown mechanism. Here we show that Fbxo7 participates in mitochondrial maintenance through direct interaction with PINK1 and Parkin and acts in Parkin-mediated mitophagy. Cells with reduced Fbxo7 expression showed deficiencies in translocation of Parkin to mitochondria, ubiquitination of mitofusin 1 and mitophagy. In Drosophila, ectopic overexpression of Fbxo7 rescued loss of Parkin, supporting a functional relationship between the two proteins. Parkinson's disease-causing mutations in Fbxo7 interfered with this process, emphasizing the importance of mitochondrial dysfunction in Parkinson's disease pathogenesis. © 2013 Nature America, Inc. All rights reserved.
CITATION STYLE
Burchell, V. S., Nelson, D. E., Sanchez-Martinez, A., Delgado-Camprubi, M., Ivatt, R. M., Pogson, J. H., … Plun-Favreau, H. (2013). The Parkinson’s disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nature Neuroscience, 16(9), 1257–1265. https://doi.org/10.1038/nn.3489
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