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

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Abstract

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.

Data availability

Matlab code for implementing the models described in this study has been made available on Github: https://github.com/lenafabr/mitoManuscriptCodes.Source data files for Figures 3, 4, 5, 6 and the appendix figure are provided in the manuscript and supporting files.

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Anamika Agrawal

Department of Physics, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1213-2321
Gulcin Pekkurnaz

Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States

For correspondence
gpekkurnaz@ucsd.edu

Competing interests
The authors declare that no competing interests exist.
Elena F Koslover

Department of Physics, University of California, San Diego, La Jolla, United States

For correspondence
ekoslover@physics.ucsd.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4139-9209

Funding

National Institutes of Health (R35GM128823)

Gulcin Pekkurnaz

Chancellor's Research Excellence Scholarship

Anamika Agrawal

Alfred P. Sloan Foundation (FG-2018-10394)

Elena F Koslover

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.