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  Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants

Klein, P., Müller-Rischart, A. K., Motori, E., Schönbauer, C., Schnorrer, F., Winklhofer, K. F., et al. (2014). Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants. The EMBO Journal, 33(4), 341-355. doi:10.1002/embj.201284290.

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Klein, Pontus1, Author              
Müller-Rischart, Anne Kathrin, Author
Motori, Elisa, Author
Schönbauer, Cornelia, Author
Schnorrer, Frank, Author
Winklhofer, Konstanze F., Author
Klein, Rüdiger1, Author              
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1Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              

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Free keywords: COMPLEX-I DEFICIENCY; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR; SIGNALING PATHWAYS; SUBSTANTIA-NIGRA; PINK1 FUNCTION; GDNF; DYSFUNCTION; MODELOXPHOS; Parkinson's disease; neurotrophic factors; neurodegeneration; Drosophila;
 Abstract: Parkinson's disease (PD)-associated Pink1 and Parkin proteins are believed to function in a common pathway controlling mitochondrial clearance and trafficking. Glial cell line-derived neurotrophic factor (GDNF) and its signaling receptor Ret are neuroprotective in toxin-based animal models of PD. However, the mechanism by which GDNF/Ret protects cells from degenerating remains unclear. We investigated whether the Drosophila homolog of Ret can rescue Pink1 and park mutant phenotypes. We report that a signaling active version of Ret (Ret(MEN)(2B)) rescues muscle degeneration, disintegration of mitochondria and ATP content of Pink1 mutants. Interestingly, corresponding phenotypes of park mutants were not rescued, suggesting that the phenotypes of Pink1 and park mutants have partially different origins. In human neuroblastoma cells, GDNF treatment rescues morphological defects of PINK1 knockdown, without inducing mitophagy or Parkin recruitment. GDNF also rescues bioenergetic deficits of PINK knockdown cells. Furthermore, overexpression of Ret(MEN)(2B) significantly improves electron transport chain complex I function in Pink1 mutant Drosophila. These results provide a novel mechanism underlying Ret-mediated cell protection in a situation relevant for human PD.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000331527900007
DOI: 10.1002/embj.201284290
 Degree: -

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Title: The EMBO Journal
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 33 (4) Sequence Number: - Start / End Page: 341 - 355 Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061_1