Spatial control of neuronal metabolism through glucose-mediated mitochondrial transport regulation

• DOI: 10.7554/elife.40986
• Publication Date: 2018-12-18T13:03:21Z
• Authors: Anamika Agrawal; Gulcin Pekkurnaz; Elena F Koslover
• Keywords: intracellular transport; 0301 basic medicine; neural metabolism; QH301-705.5; 1.1 Normal biological development and functioning; Science; Physics of Living Systems; Models, Biological; 7. Clean energy; 03 medical and health sciences; Underpinning research; Models; physics of living systems; Animals; Humans; rat; human; Biology (General); Metabolic and endocrine; Nutrition; Neurons; 0303 health sciences; Q; Neurosciences; reaction-diffusion; R; Biological Transport; mitochondrial trafficking; Biological; Axons; Mitochondria; Rats; Glucose; Medicine; Biochemistry and Cell Biology; metabolic regulation; Energy Metabolism; Algorithms

Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In rat axons, mitochondria respond to glucose levels by halting active transport in high glucose regions. We employ quantitative modeling to explore physical limits on spatial organization of mitochondria and localized metabolic enhancement through regulated stopping of processive motion. 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 estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement. Hence mitochondrial localization is shown to be a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose, as may occur in long processes of projection neurons. These findings provide a framework for the control of cellular bioenergetics through organelle trafficking.