Journal Article

DZNE-2025-00376

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.

Tutas, J.Extern* ; Tolve, M.Extern* ; Özer-Yildiz, E. ; Ickert, L. ; Klein, I. ; Silverman, Q. ; Liebsch, F. ; Dethloff, F. ; Giavalisco, P. ; Endepols, H. ; Georgomanolis, T. ; Neumaier, B. ; Drzezga, A.DZNE* ; Schwarz, G. ; Thorens, B. ; Gatto, G. ; Frezza, C. ; Kononenko, N. L.

2025
Springer Nature [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s42255-024-01196-4

Abstract: Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, autophagy is also involved in the ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during cerebellar maturation. Autophagy-deficient PCs exhibit GLUT2 accumulation on the plasma membrane, along with increased glucose uptake and alterations in glycolysis. We identify lysophosphatidic acid and serine as glycolytic intermediates that trigger PC death and demonstrate that the deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and rescues their ataxic gait. Taken together, this work reveals a mechanism for regulating GLUT2 levels in neurons and provides insights into the neuroprotective role of autophagy by controlling glucose homeostasis in the brain.

Keyword(s): Animals (MeSH) ; Autophagy-Related Protein 5: metabolism (MeSH) ; Autophagy-Related Protein 5: genetics (MeSH) ; Mice (MeSH) ; Glycolysis (MeSH) ; Autophagy (MeSH) ; Cerebellum: metabolism (MeSH) ; Purkinje Cells: metabolism (MeSH) ; Glucose: metabolism (MeSH) ; Glucose Transporter Type 2: metabolism (MeSH) ; Mice, Knockout (MeSH) ; Autophagy-Related Protein 5 ; Atg5 protein, mouse ; Glucose ; Glucose Transporter Type 2 ; Slc2a2 protein, mouse

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Contributing Institute(s):

1. Positron Emissions Tomography (PET) (AG Boecker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Tutas, J.Extern* ; Kononenko, N. L. ; Tutas, J.Extern* ; Tolve, M.Extern* ; Özer-Yildiz, E. (Researcher) ; Ickert, L. (Researcher) ; Klein, I. (Researcher) ; Silverman, Q. (Researcher) ; Liebsch, F. (Researcher) ; Dethloff, F. (Researcher) ; Giavalisco, P. (Researcher) ; Endepols, H. (Researcher) ; Georgomanolis, T. (Researcher) ; Neumaier, B. (Researcher) ; Drzezga, A. (Researcher)DZNE* ; Schwarz, G. (Researcher) ; Thorens, B. (Researcher) ; Gatto, G. (Researcher) ; Frezza, C. (Researcher) ; Kononenko, N. L. (Project Leader)
Dataset: Autophagy regulator ATG5 maintains cerebellar function by preventing its excessive glycolytic activity.
Zenodo (2024) [10.5281/zenodo.10635079]2024 BibTeX | EndNote: XML, Text | RIS

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