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@ARTICLE{Geisler:136119,
author = {Geisler, Sven and Holmström, Kira M and Treis, Angela and
Skujat, Diana and Weber, Stephanie S and Fiesel, Fabienne C
and Kahle, Philipp and Springer, Wolfdieter},
title = {{T}he {PINK}1/{P}arkin-mediated mitophagy is compromised by
{PD}-associated mutations.},
journal = {Autophagy},
volume = {6},
number = {7},
issn = {1554-8627},
address = {Abingdon, Oxon},
publisher = {Taylor $\&$ Francis},
reportid = {DZNE-2020-02441},
pages = {871-878},
year = {2010},
abstract = {Mitochondrial dysfunction is an early sign of many
neurodegenerative diseases. Very recently, two Parkinson
disease (PD) associated genes, PINK1 and Parkin, were shown
to mediate the degradation of damaged mitochondria via
selective autophagy (mitophagy). PINK1 kinase activity is
needed for prompt and efficient Parkin recruitment to
impaired mitochondria. PD-associated Parkin mutations
interfere with the process of mitophagy at distinct steps.
Here we show that whole mitochondria are turned over via
macroautophagy. Moreover, disease-associated PINK1 mutations
also compromise the selective degradation of depolarized
mitochondria. This may be due to the decreased physical
binding activity of PD-linked PINK1 mutations to Parkin.
Thus, PINK1 mutations abrogate autophagy of impaired
mitochondria upstream of Parkin. In addition to compromised
PINK1 kinase activity, reduced binding of PINK1 to Parkin
leads to failure in Parkin mitochondrial translocation,
resulting in the accumulation of damaged mitochondria, which
may contribute to disease pathogenesis.},
keywords = {Animals / Autophagy: genetics / HEK293 Cells / HeLa Cells /
Humans / Mitochondria: pathology / Mitochondria: physiology
/ Mutation / Parkinson Disease: genetics / Parkinson
Disease: pathology / Parkinson Disease: physiopathology /
Protein Kinases: genetics / Protein Kinases: metabolism /
RNA, Small Interfering: genetics / RNA, Small Interfering:
metabolism / Ubiquitin-Protein Ligases: genetics /
Ubiquitin-Protein Ligases: metabolism / RNA, Small
Interfering (NLM Chemicals) / Ubiquitin-Protein Ligases (NLM
Chemicals) / parkin protein (NLM Chemicals) / Protein
Kinases (NLM Chemicals) / PTEN-induced putative kinase (NLM
Chemicals)},
cin = {AG Kahle 2},
ddc = {570},
cid = {I:(DE-2719)1210000-4},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20798600},
doi = {10.4161/auto.6.7.13286},
url = {https://pub.dzne.de/record/136119},
}