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@INPROCEEDINGS{Zhang:145503,
author = {Zhang, L. and Whitworth, A. and Winklhofer, Konstanze F and
Schulz, J. B. and Voigt, A.},
title = {{PSM}04-06: {M}itochondrial degeneration in {PINK}1
loss-of-function isrescued by {TRAP}1},
journal = {Journal of neurochemistry},
volume = {125},
number = {Supplement 1},
issn = {0022-3042},
reportid = {DZNE-2020-00839},
pages = {142-143},
year = {2013},
abstract = {Mutations in PTEN-induced Kinase 1 (PINK1) cause
early-onsetParkinson’s disease (PD). PINK1 is critical to
maintain mitochon-drial function and protects cells from
oxidative stress by suppressingCytochrome C release and
thereby prevents cell death. Alterations inmitochondrial
integrity and function is implicated in the etiology ofPD.
It is known that application of mitochondrial toxins can
causePD. Moreover, not only PINK1-linked but also sporadic
PD patientsdisplay impaired function of mitochondrial
complex I in post-mortem brains. Recent cell culture
analysis implied that the protective effects of PINK1 are
dependent on the downstream factorTNF receptor-associated
protein 1 (TRAP1). We have recentlyshown that TRAP1
mitigates a-Synuclein induced toxicity in fliesand SH-SY5Y
cells, highlighting the importance of this protein inPD
pathology. So far, no in vivo studies on the interaction of
PINK1and TRAP1 have been reported. Here we show that human
TRAP1is able to mitigate PINK1 loss-of-function phenotypes
in flies,including morphological abnormalities, impaired
locomotion,decreased dopamine content and mitochondrial
dysfunction. Inaddition, we show that TRAP1 is able to
restore mitochondrialintegrity and function found to be
impaired in PINK1 silenced SH-SY5Y cells. Thus, our data
suggest a functional role of TRAP1 inmaintaining
mitochondrial integrity of PINK1 deficient
cells.Additionally, we provide evidence for TRAP1’s
function withinthe PINK1/Parkin pathway},
month = {Apr},
date = {2013-04-20},
organization = {24th Biennial Meeting of the
International Society for
Neurochemistry and the American Society
for Neurochemistry., Cancun (Mexico),
20 Apr 2013 - 24 Apr 2013},
cin = {AG Winklhofer},
ddc = {610},
cid = {I:(DE-2719)5000047},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
url = {https://pub.dzne.de/record/145503},
}