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 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.
Article and author information
Author details
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.
Reviewing Editor
- Raymond E Goldstein, University of Cambridge, United Kingdom
Version history
- Received: August 10, 2018
- Accepted: December 17, 2018
- Accepted Manuscript published: December 18, 2018 (version 1)
- Version of Record published: January 7, 2019 (version 2)
Copyright
© 2018, Agrawal et al.
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.
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