TY  - JOUR
A1  - Parganlija, Dajana
A1  - Klinkenberg, Michael
A1  - Domínguez-Bautista, Jorge
A1  - Hetzel, Miriam
A1  - Gispert, Suzana
A1  - Chimi, Marthe A.
A1  - Dröse, Stefan
A1  - Mai, Sören
A1  - Brandt, Ulrich
A1  - Auburger, Georg
A1  - Jendrach, Marina
T1  - Loss of PINK1 impairs stress-induced autophagy and cell survival
T2  - PLoS One
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/33455
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-334559
SN  - 1932-6203
N1  - 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.
VL  - 9
IS  - (4):e95288
PB  - PLoS
CY  - Lawrence, Kan.
ER  -