Abstract/Journal Article

DZNE-2020-00940

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Parkin: A stress-protective E3 ubiquitin ligase maintaining mitochondrial integrity

Müller-Rischart, A. K. (First author)DZNE* ; Tatzelt, J.DZNE* ; Winklhofer, K. F. (Last author)DZNE*

2012

Abstract: Mitochondrial dysfunction has long been implicated in the etiopathogenesis of Parkinson's disease (PD), based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models. Research into the function and dysfunction of PD-associated genes revealed that at least some of these genes interface with pathways regulating various aspects of mitochondrial biology. Mutations in the parkin gene, encoding an E3 ubiquitin ligase, are responsible for the majority of autosomal recessive parkinsonism. Our previous work revealed that parkin is a stress-inducible protein with a wide neuroprotective capacity, preventing cell death under various stress conditions. We now present evidence that the acute stress-protective activity of parkin and its capacity to induce mitophagy are mediated by two separate and independent pathways. While a functional autophagic machinery and expression of the mitochondrial kinase PINK1 is required for parkin-induced mitophagy, these components are dispensable for the anti-apoptotic activity of parkin. We identified a signaling pathway that is essential for the anti-apoptotic activity of parkin but not for induction of mitophagy. In support of this concept, parkin seems to exert adaptive effects on mitochondria depending on the severity of mitochondrial damage. Parkin prevents stress-induced cell death under moderate stress conditions with only minor mitochondrial defects. However, when mitochondria are irreversibly damaged in response to severe stress, parkin can promote their elimination via mitophagy.

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Contributing Institute(s):

1. Neurobiochemistry (AG Winklhofer)
2. Ext Neurobiochemistry, LMU (Ext AG Tatzelt)

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 2012

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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