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@ARTICLE{Zhu:166690,
author = {J.-Y. Zhu and S. B. Hannan$^*$ and N. Dräger$^*$ and N.
Vereshchagina and A.-C. Krahl and Y. Fu and C. J. H. Elliott
and Z. Han and T. Jahn$^*$ and T. Rasse$^*$},
title = {{A}utophagy inhibition rescues structural and functional
defects caused by the loss of mitochondrial chaperone
{H}sc70-5 in {D}rosophila.},
journal = {Autophagy},
volume = {17},
number = {10},
issn = {1554-8635},
address = {Abingdon, Oxon},
publisher = {Taylor $\&$ Francis},
reportid = {DKFZ-2021-00043},
pages = {3160-3174},
year = {2021},
note = {#LA:B180# /2021 Oct;17(10):3160-3174},
abstract = {We investigated in larval and adult Drosophila models
whether loss of the mitochondrial chaperone Hsc70-5 is
sufficient to cause pathological alterations commonly
observed in Parkinson disease. At affected larval
neuromuscular junctions, no effects on terminal size, bouton
size or number, synapse size, or number were observed,
suggesting that we studied an early stage of pathogenesis.
At this stage, we noted a loss of synaptic vesicle proteins
and active zone components, delayed synapse maturation,
reduced evoked and spontaneous excitatory junctional
potentials, increased synaptic fatigue, and cytoskeleton
rearrangements. The adult model displayed ATP depletion,
altered body posture, and susceptibility to heat-induced
paralysis. Adult phenotypes could be suppressed by knockdown
of dj-1β, Lrrk, DCTN2-p50, DCTN1-p150, Atg1, Atg101, Atg5,
Atg7, and Atg12. The knockdown of components of the
macroautophagy/autophagy machinery or overexpression of
human HSPA9 broadly rescued larval and adult phenotypes,
while disease-associated HSPA9 variants did not.
Overexpression of Pink1 or promotion of autophagy
exacerbated defects.},
keywords = {Atg1 (Other) / Hsc70-5 (Other) / microtubule (Other) /
mitochondria (Other) / mitophagy (Other) / rapamycin (Other)
/ synapse (Other)},
cin = {B180},
ddc = {570},
cid = {I:(DE-He78)B180-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33404278},
doi = {10.1080/15548627.2020.1871211},
url = {https://inrepo02.dkfz.de/record/166690},
}