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bioRxiv · 10.1101/2020.04.02.022228

The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo

Abstract

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and a considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decrease in ATP levels force cells into the stationary phase and induce autophagy. Genetic impairment of autophagy in neuroblasts using either inducible conditional mice or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration. HighlightsO_LIADP levels dynamically change during cell migration C_LIO_LIA decrease in ATP levels leads to cell pausing and autophagy induction via AMPK C_LIO_LIAutophagy is required to sustain neuronal migration by recycling focal adhesions C_LIO_LIAutophagy level is dynamically modulated by migration-promoting and inhibiting cues C_LI

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Bressan, C., Pecora, A., Gagnon, D., Snapyan, M., Labrecque, S., De Koninck, P., Parent, M., Saghatelyan, A.. 2020-04-04. The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo. https://doi.org/10.1101/2020.04.02.022228

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