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The Biogeography of Neuronal Metabolism
The topological compartmentalization of metabolic pathways defines the physical delimitation of metabolic fluxes within the cytoplasm. Thus, spatiotemporal regulation of metabolism is critical for cellular functions, especially for highly polarized neurons. We investigate the molecular mechanisms orchestrating metabolic enzyme compartmentalization for efficient energy generation in neurons by using live-cell imaging, genetically encoded metabolite sensors and metabolic flux analysis.
Metabolic regulation of organelles
All cells contain hundreds of organelles, which work together to maintain metabolic homeostasis. Metabolic flux sensitive post-translational modification, O-GlcNAcylation, uniquely couples nutrient status to mitochondrial dynamics. We study how O-GlcNAc modification regulates the relationship between organelles, organelle-interactions, positioning, function, and cellular metabolism. We utilize a wide array of approaches, combining proteomics, microscopy, and metabolic flux analysis to study the metabolic regulation of organelles in neurons and other cells.
Neuron-type specific mitochondrial programming
The function of mitochondria is hard-wired to cellular metabolism. In the context of the brain, where cellular diversity is extremely complex, this raises many important questions. We are deconstructing the mitochondrial properties from genetically defined cell classes in the nervous system by using Cre-dependent viral tagging and proteomics approaches. Our interdisciplinary approach is poised to reveal fundamental insights into the mechanisms that regulate neuronal bioenergetics and pinpoint the underlying causes of energy impairments that lead to neurological diseases.
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