%0 Journal Article
%A Müller-Rischart, A. Kathrin
%A Pilsl, Anna
%A Beaudette, Patrick
%A Patra, Maria
%A Hadian, Kamyar
%A Funke, Maria
%A Peis, Regina
%A Deinlein, Alexandra
%A Schweimer, Carolin
%A Kuhn, Peer-Hendrik
%A Lichtenthaler, Stefan F
%A Motori, Elisa
%A Hrelia, Silvana
%A Wurst, Wolfgang
%A Trümbach, Dietrich
%A Langer, Thomas
%A Krappmann, Daniel
%A Dittmar, Gunnar
%A Tatzelt, Jörg
%A Winklhofer, Konstanze F
%T The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO.
%J Molecular cell
%V 49
%N 5
%@ 1097-2765
%C New York, NY
%I Elsevier
%M DZNE-2020-03161
%P 908-921
%D 2013
%X 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.
%K Animals
%K Apoptosis
%K Fibroblasts: metabolism
%K HEK293 Cells
%K Humans
%K Intracellular Signaling Peptides and Proteins: genetics
%K Intracellular Signaling Peptides and Proteins: metabolism
%K Mice
%K Mice, Knockout
%K Mitochondria: metabolism
%K NF-kappa B: genetics
%K NF-kappa B: metabolism
%K Neurons: metabolism
%K Parkinson Disease: genetics
%K Parkinson Disease: metabolism
%K Signal Transduction
%K Transfection
%K Ubiquitin-Protein Ligases: genetics
%K Ubiquitin-Protein Ligases: metabolism
%K Ubiquitination: genetics
%K Intracellular Signaling Peptides and Proteins (NLM Chemicals)
%K NEMO protein, mouse (NLM Chemicals)
%K NF-kappa B (NLM Chemicals)
%K Ubiquitin-Protein Ligases (NLM Chemicals)
%K parkin protein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23453807
%R 10.1016/j.molcel.2013.01.036
%U https://pub.dzne.de/record/136839