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@ARTICLE{MllerRischart:136839,
author = {Müller-Rischart, A. Kathrin and Pilsl, Anna and Beaudette,
Patrick and Patra, Maria and Hadian, Kamyar and Funke, Maria
and Peis, Regina and Deinlein, Alexandra and Schweimer,
Carolin and Kuhn, Peer-Hendrik and Lichtenthaler, Stefan F
and Motori, Elisa and Hrelia, Silvana and Wurst, Wolfgang
and Trümbach, Dietrich and Langer, Thomas and Krappmann,
Daniel and Dittmar, Gunnar and Tatzelt, Jörg and
Winklhofer, Konstanze F},
title = {{T}he {E}3 ligase parkin maintains mitochondrial integrity
by increasing linear ubiquitination of {NEMO}.},
journal = {Molecular cell},
volume = {49},
number = {5},
issn = {1097-2765},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2020-03161},
pages = {908-921},
year = {2013},
abstract = {Parkin, a RING-between-RING-type E3 ubiquitin ligase
associated with Parkinson's disease, has a wide
neuroprotective activity, preventing cell death in various
stress paradigms. We identified a stress-protective pathway
regulated by parkin that links NF-κB signaling and
mitochondrial integrity via linear ubiquitination. Under
cellular stress, parkin is recruited to the linear ubiquitin
assembly complex and increases linear ubiquitination of
NF-κB essential modulator (NEMO), which is essential for
canonical NF-κB signaling. As a result, the mitochondrial
guanosine triphosphatase OPA1 is transcriptionally
upregulated via NF-κB-responsive promoter elements for
maintenance of mitochondrial integrity and protection from
stress-induced cell death. Parkin-induced stress protection
is lost in the absence of either NEMO or OPA1, but not in
cells defective for the mitophagy pathway. Notably, in
parkin-deficient cells linear ubiquitination of NEMO,
activation of NF-κB, and upregulation of OPA1 are
significantly reduced in response to TNF-α stimulation,
supporting the physiological relevance of parkin in
regulating this antiapoptotic pathway.},
keywords = {Animals / Apoptosis / Fibroblasts: metabolism / HEK293
Cells / Humans / Intracellular Signaling Peptides and
Proteins: genetics / Intracellular Signaling Peptides and
Proteins: metabolism / Mice / Mice, Knockout / Mitochondria:
metabolism / NF-kappa B: genetics / NF-kappa B: metabolism /
Neurons: metabolism / Parkinson Disease: genetics /
Parkinson Disease: metabolism / Signal Transduction /
Transfection / Ubiquitin-Protein Ligases: genetics /
Ubiquitin-Protein Ligases: metabolism / Ubiquitination:
genetics / Intracellular Signaling Peptides and Proteins
(NLM Chemicals) / NEMO protein, mouse (NLM Chemicals) /
NF-kappa B (NLM Chemicals) / Ubiquitin-Protein Ligases (NLM
Chemicals) / parkin protein (NLM Chemicals)},
cin = {AG Lichtenthaler / AG Wurst},
ddc = {610},
cid = {I:(DE-2719)1110006 / I:(DE-2719)1140001},
pnm = {341 - Molecular Signaling (POF3-341) / 342 - Disease
Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23453807},
doi = {10.1016/j.molcel.2013.01.036},
url = {https://pub.dzne.de/record/136839},
}