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PLoS Comput Biol. 2017 Apr 17;13(4):e1005458. doi: 10.1371/journal.pcbi.1005458. eCollection 2017 Apr.

Achieving global perfect homeostasis through transporter regulation.

Author information

1
Department of Physiology, Biophysics and Systems Biology, Faculty of Medicine, Technion, Haifa, Israel.
2
Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia.
3
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.

Abstract

Nutrient homeostasis-the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments-is essential to the survival of most organisms. Transcriptional regulation of plasma membrane transporters by internal nutrient concentrations is typically assumed to be the main mechanism by which homeostasis is achieved. While this mechanism is homeostatic we show that it does not achieve global perfect homeostasis-a condition where internal nutrient concentrations are completely independent of external nutrient concentrations for all external nutrient concentrations. We show that the criterion for global perfect homeostasis is that transporter levels must be inversely proportional to net nutrient flux into the cell and that downregulation of active transporters (activity-dependent regulation) is a simple and biologically plausible mechanism that meets this criterion. Activity-dependent transporter regulation creates a trade-off between robustness and efficiency, i.e., the system's ability to withstand perturbation in external nutrients and the transporter production rate needed to maintain homeostasis. Additionally, we show that a system that utilizes both activity-dependent transporter downregulation and regulation of transporter synthesis by internal nutrient levels can create a system that mitigates the shortcomings of each of the individual mechanisms. This analysis highlights the utility of activity-dependent regulation in achieving homeostasis and calls for a re-examination of the mechanisms of regulation of other homeostatic systems.

PMID:
28414718
PMCID:
PMC5411106
DOI:
10.1371/journal.pcbi.1005458
[Indexed for MEDLINE]
Free PMC Article

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