Loss of PINK1 impairs stress-induced autophagy and cell survival

  • The mitochondrial kinase PINK1 and the ubiquitin ligase Parkin are participating in quality control after CCCP- or ROSinduced mitochondrial damage, and their dysfunction is associated with the development and progression of Parkinson’s disease. Furthermore, PINK1 expression is also induced by starvation indicating an additional role for PINK1 in stress response. Therefore, the effects of PINK1 deficiency on the autophago-lysosomal pathway during stress were investigated. Under trophic deprivation SH-SY5Y cells with stable PINK1 knockdown showed downregulation of key autophagic genes, including Beclin, LC3 and LAMP-2. In good agreement, protein levels of LC3-II and LAMP-2 but not of LAMP-1 were reduced in different cell model systems with PINK1 knockdown or knockout after addition of different stressors. This downregulation of autophagic factors caused increased apoptosis, which could be rescued by overexpression of LC3 or PINK1. Taken together, the PINK1-mediated reduction of autophagic key factors during stress resulted in increased cell death, thus defining an additional pathway that could contribute to the progression of Parkinson’s disease in patients with PINK1 mutations.

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Author:Dajana Parganlija, Michael Klinkenberg, Jorge Domínguez-Bautista, Miriam Hetzel, Suzana Gispert, Marthe A. Chimi, Stefan DröseORCiDGND, Sören Mai, Ulrich BrandtORCiDGND, Georg AuburgerORCiDGND, Marina Jendrach
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24751806
Parent Title (English):PLoS One
Place of publication:Lawrence, Kan.
Document Type:Article
Date of Publication (online):2014/04/21
Date of first Publication:2014/04/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/05/07
Page Number:13
Copyright: © 2014 Parganlija et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0