Vesicular glycolysis provides on-board energy for fast axonal transport.

Diana Zala, Maria-Victoria Hinckelmann, Hua Yu, Marcel Menezes Lyra da Cunha, Géraldine Liot, Fabrice P. Cordelières, Sergio Marco, Frédéric Saudou
Cell. 2013-01-01; 152(3): 479-491
DOI: 10.1016/j.cell.2012.12.029

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1. Cell. 2013 Jan 31;152(3):479-91. doi: 10.1016/j.cell.2012.12.029.

Vesicular glycolysis provides on-board energy for fast axonal transport.

Zala D(1), Hinckelmann MV, Yu H, Lyra da Cunha MM, Liot G, Cordelières FP, Marco
S, Saudou F.

Author information:
(1)Institut Curie, 91405 Orsay, France.

Comment in
Nat Rev Neurosci. 2013 Mar;14(3):156.

Fast axonal transport (FAT) requires consistent energy over long distances to
fuel the molecular motors that transport vesicles. We demonstrate that glycolysis
provides ATP for the FAT of vesicles. Although inhibiting ATP production from
mitochondria did not affect vesicles motility, pharmacological or genetic
inhibition of the glycolytic enzyme GAPDH reduced transport in cultured neurons
and in Drosophila larvae. GAPDH localizes on vesicles via a huntingtin-dependent
mechanism and is transported on fast-moving vesicles within axons. Purified
motile vesicles showed GAPDH enzymatic activity and produced ATP. Finally, we
show that vesicular GAPDH is necessary and sufficient to provide on-board energy
for fast vesicular transport. Although detaching GAPDH from vesicles reduced
transport, targeting GAPDH to vesicles was sufficient to promote FAT in GAPDH
deficient neurons. This specifically localized glycolytic machinery may supply
constant energy, independent of mitochondria, for the processive movement of
vesicles over long distances in axons.

Copyright © 2013 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.cell.2012.12.029
PMID: 23374344 [Indexed for MEDLINE]

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