NEUROMITO · Mitochondrial Dynamics and Local Protein Synthesis in Dendrites

Mitochondrial Dynamics and Local Protein Synthesis in Dendrites

The human brain consumes 20% of the total energy in the body while it constitutes only 2% of the body weight. Particularly, proteostasis and modifying synaptic proteomes represent a large energy demand during synaptic plasticity and little is known on how the energy demands are met locally at dendrites and spines. Mitochondria, the powerhouses of cells, are found in neuronal compartments, but their molecular regulation in response to neuronal energy demands and their role in fueling local neuronal function remains largely unaddressed. During my Marie Curie Individual postdoctoral fellowship, I investigated the significance of mitochondria in local translation in the Schuman group, employing state-of-the-art imaging, proteomics and transcriptomic methodologies developed in the lab. The overall goal of the project was to elucidate the significance of mitochondria during high-energy demands of local protein synthesis with the following objectives: i) investigate mitochondrial compartmentalization and its activity-dependence in local dendritic translation; and ii) analyse mitochondrial proteomics and transcriptomics during synaptic plasticity. By refining and pushing the limits of conventional and super-resolution microscopy to image live dendritic mitochondria, experimentally manipulate local mitochondrial function in dendrites, label and visualize newly synthesized proteins in response to synaptic stimulation, I have demonstrated that: mitochondria exist in spatially stable compartments in dendrites and serve as local energy reserves to fuel synaptic protein synthesis during synaptic activity. These findings have revealed that in addition to the presence of localized translational machinery in dendrites, local compartments of energy exist, thereby opening up new unexplored questions on synaptic plasticity and metabolism. In order to further investigate how the mitochondrial proteome is modulated during synaptic plasticity, I employed a previously reported strategy for labeling and isolation of the sub mitochondrial proteome, characterized and established it as a tool to examine the neuronal mitochondrial proteome and its regulation during neuronal activity.

Data: CORDIS, © European Union