Journal Article

DZNE-2020-03161

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO.

Müller-Rischart, A. K.DZNE* ; Pilsl, A. ; Beaudette, P. ; Patra, M. ; Hadian, K. ; Funke, M. ; Peis, R. ; Deinlein, A. ; Schweimer, C. ; Kuhn, P.-H.DZNE* ; Lichtenthaler, S. F.DZNE* ; Motori, E. ; Hrelia, S. ; Wurst, W.DZNE* ; Trümbach, D. ; Langer, T. ; Krappmann, D. ; Dittmar, G. ; Tatzelt, J.DZNE* ; Winklhofer, K. F. (Last author)DZNE*

2013
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.molcel.2013.01.036

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.

Keyword(s): Animals (MeSH) ; Apoptosis (MeSH) ; Fibroblasts: metabolism (MeSH) ; HEK293 Cells (MeSH) ; Humans (MeSH) ; Intracellular Signaling Peptides and Proteins: genetics (MeSH) ; Intracellular Signaling Peptides and Proteins: metabolism (MeSH) ; Mice (MeSH) ; Mice, Knockout (MeSH) ; Mitochondria: metabolism (MeSH) ; NF-kappa B: genetics (MeSH) ; NF-kappa B: metabolism (MeSH) ; Neurons: metabolism (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Signal Transduction (MeSH) ; Transfection (MeSH) ; Ubiquitin-Protein Ligases: genetics (MeSH) ; Ubiquitin-Protein Ligases: metabolism (MeSH) ; Ubiquitination: genetics (MeSH) ; Intracellular Signaling Peptides and Proteins ; NEMO protein, mouse ; NF-kappa B ; Ubiquitin-Protein Ligases ; parkin protein

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)
2. Genome Engineering (AG Wurst)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)
2. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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