TY  - CONF
AU  - Müller-Rischart, Anne Kathrin
AU  - Pilsl, Anna
AU  - Bouman, Lena
AU  - Tatzelt, Jörg
AU  - Winklhofer, Konstanze F
TI  - Parkinson's disease-associated genes and mitochondrial integrity
JO  - Biochimica et biophysica acta / Bioenergetics
VL  - 1797
SN  - 0005-2728
M1  - DZNE-2020-00768
SP  - 75
PY  - 2010
AB  - Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer's disease, affecting an increasing number of patients due to the demographic trend towards an aged population. Oxidative stress, mitochondrial dysfunction and protein aggregation are pathophysiological alterations consistently found in the course of the disease, however, the etiology of sporadic PD still remains enigmatic. Thus, the identification of genes which are reponsible for familial variants was a major breakthrough. Importantly, several PD-linked gene products have a direct or indirect impact on mitochondrial integrity, emphasizing a crucial role of mitochondria in the pathogenesis of PD. Loss-of-function mutations in the E3 ubiquitin ligase parkin or the mitochondrial kinase PINK1 are associated with autosomal recessive parkinsonism. Our previous work revealed that parkin is a stress-responsive protein with a remarkably wide neuroprotective capacity, preventing cell death under various stress conditions. An early consequence of parkin or PINK1 silencing in human cells is a decrease in mitochondrial membrane potential and ATP production and increase in mitochondrial fragmentation. Remarkably, parkin can increase the clearance of dysfunctional mitochondria by mitophagy in a PINK1-dependent manner. We will discuss the underlying mechanisms and present data indicative of a regulatory crosstalk between the autophagic machinery and mitochondrial dynamics.
T2  - 16th European Bioenergetics Conference
CY  - 17 Jul 2010 - 22 Jul 2010,  ()
Y2  - 17 Jul 2010 - 22 Jul 2010
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
UR  - https://pub.dzne.de/record/145425
ER  -