The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
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The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions. / Lanfranchi, Marine; Yandiev, Sozerko; Meyer-Dilhet, Géraldine; Ellouze, Salma; Kerkhofs, Martijn; Dos Reis, Raphael; Garcia, Audrey; Blondet, Camille; Amar, Alizée; Kneppers, Anita; Polvèche, Hélène; Plassard, Damien; Foretz, Marc; Viollet, Benoit; Sakamoto, Kei; Mounier, Rémi; Bourgeois, Cyril F.; Raineteau, Olivier; Goillot, Evelyne; Courchet, Julien.
In: Nature Communications, Vol. 15, 2487, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
AU - Lanfranchi, Marine
AU - Yandiev, Sozerko
AU - Meyer-Dilhet, Géraldine
AU - Ellouze, Salma
AU - Kerkhofs, Martijn
AU - Dos Reis, Raphael
AU - Garcia, Audrey
AU - Blondet, Camille
AU - Amar, Alizée
AU - Kneppers, Anita
AU - Polvèche, Hélène
AU - Plassard, Damien
AU - Foretz, Marc
AU - Viollet, Benoit
AU - Sakamoto, Kei
AU - Mounier, Rémi
AU - Bourgeois, Cyril F.
AU - Raineteau, Olivier
AU - Goillot, Evelyne
AU - Courchet, Julien
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.
AB - The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.
U2 - 10.1038/s41467-024-46146-6
DO - 10.1038/s41467-024-46146-6
M3 - Journal article
C2 - 38514619
AN - SCOPUS:85188336088
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2487
ER -
ID: 388034153