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Drosophila Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin

Ziviani, E., Tao, R.N. and Whitworth, A.J. (2010) Drosophila Parkin requires PINK1 for mitochondrial translocation and ubiquitinates Mitofusin. Proceedings of the National Academy of Sciences of the United States of America , 107 (11). pp. 5018-5023. ISSN 0027-8424

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Abstract

Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology. Parkin has been linked to multiple cellular processes including protein degradation, mitochondrial homeostasis, and autophagy; however, its precise role in pathogenesis is unclear. Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover. The precise mechanism of recruitment and the ubiquitination target are unclear. Here we show in Drosophila cells that PINK1 is required to recruit Parkin to dysfunctional mitochondria and promote their degradation. Furthermore, PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria. Loss of Drosophila PINK1 or parkin causes an increase in Mfn abundance in vivo and concomitant elongation of mitochondria. These findings provide a molecular mechanism by which the PINK1/Parkin pathway affects mitochondrial fission/fusion as suggested by previous genetic interaction studies. We hypothesize that Mfn ubiquitination may provide a mechanism by which terminally damaged mitochondria are labeled and sequestered for degradation by autophagy.

Item Type: Article
Copyright, Publisher and Additional Information: © 2010 National Academy of Sciences. This is an author produced version of a paper subsequently published in Proceedings of the National Academy of Sciences of the United States of America. Uploaded in accordance with the publisher's self-archiving policy.
Keywords: mitophagy; neurodegeneration; Parkinson's disease; quality control
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield) > Centre for Developmental Genetics (Sheffield)
The University of Sheffield > University of Sheffield Research Centres and Institutes > Centre for Developmental Genetics (Sheffield)

The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 23 Apr 2010 09:57
Last Modified: 08 Feb 2013 17:00
Published Version: http://dx.doi.org/10.1073/pnas.0913485107
Status: Published
Publisher: National Academy of Sciences
Refereed: Yes
Identification Number: 10.1073/pnas.0913485107
URI: http://eprints.whiterose.ac.uk/id/eprint/10759

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