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@ARTICLE{Klein:137272,
author = {Klein, Pontus and Müller-Rischart, Anne Kathrin and
Motori, Elisa and Schönbauer, Cornelia and Schnorrer, Frank
and Winklhofer, Konstanze F and Klein, Rüdiger},
title = {{R}et rescues mitochondrial morphology and muscle
degeneration of {D}rosophila {P}ink1 mutants.},
journal = {The EMBO journal},
volume = {33},
number = {4},
issn = {0261-4189},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2020-03594},
pages = {341-355},
year = {2014},
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(MEN₂B) 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(MEN₂B) 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.},
keywords = {Adenosine Triphosphate: metabolism / Animals / Apoptosis /
Autophagy / Cell Line, Tumor / Disease Models, Animal /
Dopamine: metabolism / Drosophila Proteins: deficiency /
Drosophila Proteins: genetics / Drosophila Proteins:
physiology / Drosophila melanogaster: genetics / Drosophila
melanogaster: growth $\&$ development / Electron Transport
Complex I: physiology / Genes, Lethal / Glial Cell
Line-Derived Neurotrophic Factor: pharmacology / Humans /
Mitochondria, Muscle: ultrastructure / Muscular Atrophy:
prevention $\&$ control / Neuroblastoma: pathology /
Neurons: ultrastructure / Oxygen Consumption / Parkinson
Disease / Phenotype / Protein Kinases: deficiency / Protein
Kinases: genetics / Protein-Serine-Threonine Kinases:
deficiency / Protein-Serine-Threonine Kinases: genetics /
Protein-Serine-Threonine Kinases: physiology /
Proto-Oncogene Proteins c-ret: genetics / Proto-Oncogene
Proteins c-ret: physiology / Pupa / Signal Transduction:
physiology / Ubiquitin-Protein Ligases: deficiency /
Ubiquitin-Protein Ligases: genetics / Drosophila Proteins
(NLM Chemicals) / Glial Cell Line-Derived Neurotrophic
Factor (NLM Chemicals) / Adenosine Triphosphate (NLM
Chemicals) / Ubiquitin-Protein Ligases (NLM Chemicals) /
Protein Kinases (NLM Chemicals) / Proto-Oncogene Proteins
c-ret (NLM Chemicals) / Ret protein, Drosophila (NLM
Chemicals) / PINK1 protein, Drosophila (NLM Chemicals) /
PTEN-induced putative kinase (NLM Chemicals) /
Protein-Serine-Threonine Kinases (NLM Chemicals) / park
protein, Drosophila (NLM Chemicals) / Electron Transport
Complex I (NLM Chemicals) / Dopamine (NLM Chemicals)},
cin = {AG Winklhofer},
ddc = {570},
cid = {I:(DE-2719)5000047},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24473149},
pmc = {pmc:PMC3983680},
doi = {10.1002/embj.201284290},
url = {https://pub.dzne.de/record/137272},
}