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@ARTICLE{Tutas:1039733,
author = {Tutas, Janine and Tolve, Marianna and Özer-Yildiz, Ebru
and Ickert, Lotte and Klein, Ines and Silverman, Quinn and
Liebsch, Filip and Dethloff, Frederik and Giavalisco,
Patrick and Endepols, Heike and Georgomanolis, Theodoros and
Neumaier, Bernd and Drzezga, Alexander and Schwarz, Guenter
and Thorens, Bernard and Gatto, Graziana and Frezza,
Christian and Kononenko, Natalia L.},
title = {{A}utophagy regulator {ATG}5 preserves cerebellar function
by safeguarding its glycolytic activity},
journal = {Nature metabolism},
volume = {7},
issn = {2522-5812},
address = {[London]},
publisher = {Springer Nature},
reportid = {FZJ-2025-01777},
pages = {297–320},
year = {2025},
abstract = {Dysfunctions in autophagy, a cellular mechanism for
breaking downcomponents within lysosomes, often lead to
neurodegeneration. Thespecific mechanisms underlying
neuronal vulnerability due to autophagydysfunction remain
elusive. Here we show that autophagy contributesto
cerebellar Purkinje cell (PC) survival by safeguarding their
glycolyticactivity. Outside the conventional housekeeping
role, autophagy is alsoinvolved in the ATG5-mediated
regulation of glucose transporter 2 (GLUT2)levels during
cerebellar maturation. Autophagy-deficient PCs exhibitGLUT2
accumulation on the plasma membrane, along with
increasedglucose uptake and alterations in glycolysis. We i
de nt ify l ys op hosp ha-tidic acid and serine as
glycolytic intermediates that trigger PC death
anddemonstrate that the deletion of GLUT2 in ATG5-deficient
mice mitigates PCne urod egen e ration and rescues their
ataxic gait. Taken together, this workreveals a mechanism
for regulating GLUT2 levels in neurons and providesinsights
into the neuroprotective role of autophagy by controlling
glucosehomeostasis in the brain.},
cin = {INM-5 / INM-2},
ddc = {610},
cid = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {39815080},
UT = {WOS:001396167500001},
doi = {10.1038/s42255-024-01196-4},
url = {https://juser.fz-juelich.de/record/1039733},
}