2. Academic Validation
  3. The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy

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

  • Nat Neurosci. 2013 Sep;16(9):1257-65. doi: 10.1038/nn.3489.
Victoria S Burchell 1,  David E Nelson,  Alvaro Sanchez-Martinez,  Marta Delgado-Camprubi,  Rachael M Ivatt,  Joe H Pogson,  Suzanne J Randle,  Selina Wray,  Patrick A Lewis,  Henry Houlden,  Andrey Y Abramov,  John Hardy,  Nicholas W Wood,  Alexander J Whitworth,  Heike Laman,  Helene Plun-Favreau
Affiliations

Affiliation

  • 1 Department of Molecular Neuroscience, University College London Institute of Neurology, London, UK.
PMID: 23933751 DOI: 10.1038/nn.3489
Abstract

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.

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