Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin.

TitleDrosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin.
Publication TypeJournal Article
Year of Publication2010
AuthorsZiviani, E, Tao, RN, Whitworth, AJ
JournalProc Natl Acad Sci U S A
Volume107
Issue11
Pagination5018-23
Date Published2010 Mar 16
ISSN1091-6490
KeywordsAnimals, Autophagy, Drosophila melanogaster, Drosophila Proteins, Gene Knockdown Techniques, Membrane Proteins, Mitochondria, Mutation, Protein Transport, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, Ubiquitination
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.

DOI10.1073/pnas.0913485107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.0913485107
PubMed ID20194754
PubMed Central IDPMC2841909
Grant List081987 / / Wellcome Trust / United Kingdom
081987 / / Wellcome Trust / United Kingdom
G-0713 / / Parkinson's UK / United Kingdom
G070091 / / Medical Research Council / United Kingdom
GR077544AIA / / Wellcome Trust / United Kingdom