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SynaptoEnergy

Financiado
Molecular physiology of nerve terminal bioenergetics
Synaptic transmission is an extremely energetically-demanding process that consumes 75% of the energy required for brain function. However, it remains poorly understood how synapses guarantee the necessary ATP levels required for... Synaptic transmission is an extremely energetically-demanding process that consumes 75% of the energy required for brain function. However, it remains poorly understood how synapses guarantee the necessary ATP levels required for neurotransmission. While our understanding of the metabolic pathways for ATP production is vastly detailed, very little is known about the actual molecular implementation of these pathways in neurons for sustaining synaptic bioenergetics. I hypothesize that tightly-regulated control mechanisms exist presynaptically to ensure the molecular activation of glycolysis and oxidative phosphorylation (OxPhos) on demand, optimally coupling local ATP synthesis to consumption thereby maintaining synaptic metabolic integrity and safeguarding presynaptic function. Here I propose to develop a comprehensive molecular understanding of the mechanisms controlling these pathways in firing synapses. I will use cutting-edge optophysiology tools that I and others have developed to study neuronal bioenergetics together with novel proteomic approaches to identify key molecules involved in controlling presynaptic OxPhos and glycolysis. First, I will dissect the fundamental mechanisms controlling Ca2+-mediated activation of OxPhos in presynaptic mitochondria during synaptic activity. To further elucidate the presynaptic choreography of molecular mechanisms enhancing glycolysis rates on demand, I will dissect the mechanistic control of the presynaptic glucose carrier GLUT4 and establish the role of glycolytic metabolons in accelerating glycolysis during synaptic activity. By generating for the first time a comprehensive picture of the molecular mechanisms actively maintaining presynaptic metabolic integrity, this study will provide a framework for future studies into the molecular basis of brain disease states associated with dysfunctional metabolism, such as mitochondriopathies, vascular dementias or glucose metabolism diseases. ver más
30/06/2025
MINISTERE DE L'ENS...
1M€
Perfil tecnológico estimado
Duración del proyecto: 67 meses Fecha Inicio: 2019-11-05
Fecha Fin: 2025-06-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2019-11-05
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG: ERC Starting Grant
Cerrada hace 6 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
MINISTERE DE L'ENSEIGNEMENT SUPERIEUR ET DE... No se ha especificado una descripción o un objeto social para esta compañía.