TY  - JOUR
A1  - Klinkenberg, Michael
A1  - Gispert, Suzana
A1  - Dominguez Bautista, Jorge Antolio
A1  - Braun, Isabelle
A1  - Auburger, Georg
A1  - Jendrach, Marina
T1  - Restriction of trophic factors and nutrients induces PARKIN expression
T2  - Neurogenetics
N2  - Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder and manifests at old age. While many details of its pathogenesis remain to be elucidated, in particular the protein and mitochondrial quality control during stress responses have been implicated in monogenic PD variants. Especially the mitochondrial kinase PINK1 and the ubiquitin ligase PARKIN are known to cooperate in autophagy after mitochondrial damage. As autophagy is also induced by loss of trophic signaling and PINK1 gene expression is modulated after deprivation of cytokines, we analyzed to what extent trophic signals and starvation stress regulate PINK1 and PARKIN expression. Time course experiments with serum deprivation and nutrient starvation of human SH-SY5Y neuroblastoma cells and primary mouse neurons demonstrated phasic induction of PINK1 transcript up to twofold and PARKIN transcript levels up to sixfold. The corresponding threefold starvation induction of PARKIN protein was limited by its translocation to lysosomes. Analysis of primary mouse cells from PINK1-knockout mice indicated that PARKIN induction and lysosomal translocation occurred independent of PINK1. Suppression of the PI3K-Akt-mTOR signaling by pharmacological agents modulated PARKIN expression accordingly. In conclusion, this expression survey demonstrates that PARKIN and PINK1 are coregulated during starvation and suggest a role of both PD genes in response to trophic signals and starvation stress.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29905
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-299055
SN  - 1364-6753
SN  - 1364-6745
N1  - (c) The Author(s) 2011. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
VL  - 13
IS  - 1
SP  - 9
EP  - 21
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -