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.
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The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy.pdf - Accepted Version Download (5MB) | Preview |
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.
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