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| Home > Publications database > Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity |
| Home > Publications database > Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity |
| Journal Article | FZJ-2025-01777 |
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2025
Springer Nature
[London]
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Please use a persistent id in citations: doi:10.1038/s42255-024-01196-4 doi:10.34734/FZJ-2025-01777
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.
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