Periodic Reporting for period 2 - SynaptoEnergy (Molecular physiology of nerve terminal bioenergetics)
Berichtszeitraum: 2021-07-01 bis 2022-12-31
On the other hand, our project has progressed in better understanding how neurons can preserve their energy levels independently of mitochondria, allowing them to transmit information and preserve brain function. ATP, the main molecular fuel of neuronal communication, can be obtained by two main processes: glycolysis (using glucose) or mitochondrial oxidative phosphorylation (which uses oxygen and other substrates). Our main results for this first period of the grant have been focused on oxidative phosphorylation, which is a process driven by mitochondria. However, to better understand the molecular mechanisms facilitating glucose use by neurons, we have developed novel molecular technologies that allow seeing how many glucose transporters are in synapses, the regions of the neurons that communicate information. The surface of a synapse is decorated with a large variety of molecules that facilitate neuronal communication. One of these molecules is called GLUT4, which is a protein that has the ability of transporting glucose inside the neuron. Intuitively, the higher the number of these transporters, the better the ability of a synapse to capture surrounding glucose to facilitate its function. However, understanding quantitatively how many proteins of a particular type are present in the surface of a synapse, and whether this number can change dynamically depending on the needs, remains poorly understood. We have developed novel technologies that allow isolating all proteins present in the synaptic surface, both at rest or during neurotransmission, allowing to understand how surface proteins adapt to the activity of the neuron. This now includes GLUT4, but it is a novel technology that expands what could be studied before and can provide a holistic picture of how the surface landscape of synapses changes when neurons talk to each other.