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The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy

Burchell, VS; Nelson, DE; Sanchez-Martinez, A; Delgado-Camprubi, M; Ivatt, RM; Pogson, JH; Randle, SJ; ... Plun-Favreau, H; + view all (2013) The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nature Neuroscience , 16 (9) pp. 1257-1265. 10.1038/nn.3489. Green open access

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Abstract

ompelling 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.

Type: Article
Title: The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nn.3489
Publisher version: http://dx.doi.org/10.1038/nn.3489
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, F-BOX PROTEIN, MITOCHONDRIAL PATHOLOGY, MONITORING AUTOPHAGY, TARGETING SEQUENCES, PYRAMIDAL SYNDROME, DROSOPHILA, PINK1, COMPLEX, CELLS, PROTEASOME
URI: http://discovery.ucl.ac.uk/id/eprint/1402042
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