Effect of Glucose-dependent Motility on Spatial Organization of Mitochondria in a Neuron

Cellular metabolism has been a focus of intense study since the early days of molecular biology. The standard quantitative methods that have been developed for modeling metabolic response generally neglect intracellular spatial organization. Carefully regulated distribution of metabolic components is especially critical for the time-sensitive energy demands of hyper-extended cells like the neuron. Recent experimental results have shown that the transport of mitochondria is regulated by glucose concentration, and that glucose itself is heterogeneously distributed in neurons. We use analytical methods and simulations to model glucose-dependent mitochondrial motility in a neuron with spatially varying permeability to extracellular glucose. Our model encapsulates biochemical pathways coupling the action of molecular motors responsible for mitochondrial transport to glucose concentration via nonlinear kinetics. The resulting distribution of mitochondria suggests that transport-based regulation can be made sensitive to a broad range of glucose levels under sufficiently rapid rates of glucose consumption by mitochondria. Our predictions for these sensitivity ranges are parameterized by and validated against in vivo data on neuronal mitochondria distribution.