Spatial Control of Neuronal Metabolism Through Glucose-Mediated Mitochondrial Transport Regulation

Abstract

Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In the axons of mammalian neurons, mitochondria have been shown to respond to glucose levels by halting active transport preferentially in high glucose regions. Here, we employ quantitative modeling to explore the physical limits on spatial organization of organelles through such regulated stopping of processive motion, as well as the consequences to cellular metabolism. We delineate the role of key parameters, including cellular glucose uptake and consumption rates, that are expected to modulate mitochondrial distribution and metabolic response in spatially varying glucose conditions. Our quantitative estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement, making this a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose. These findings highlight the role of spatial organization in the regulation of neuronal metabolism, while providing a quantitative framework for the establishment of such organization by control of organelle trafficking.