TY  - CONF
AU  - Müller-Rischart, Anne Kathrin
AU  - Tatzelt, Jörg
AU  - Winklhofer, Konstanze F
TI  - Parkin: A stress-protective E3 ubiquitin ligase maintaining mitochondrial integrity
JO  - Biochimica et biophysica acta / Bioenergetics
VL  - 1817
IS  - Sup
SN  - 0005-2728
M1  - DZNE-2020-00940
SP  - S77 - S78
PY  - 2012
AB  - 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.
T2  - 17th European Bioenergetics Conference (EBEC)
CY  - 15 Sep 2012 - 20 Sep 2012, Freiburg (Germany)
Y2  - 15 Sep 2012 - 20 Sep 2012
M2  - Freiburg, Germany
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
UR  - https://pub.dzne.de/record/145610
ER  -