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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Achieving global perfect homeostasis through transporter regulation
Yonatan Savir1, Alexander Martynov2,3, Michael Springer3
1Department of Physiology, Biophysics and Systems Biology, Faculty of Medicine, Technion, Haifa, Israel.
Plos Computational Biology
|April 18, 2017
Summary
Nutrient homeostasis is vital for survival. Activity-dependent transporter regulation, not just internal nutrient sensing, is key to achieving perfect nutrient balance, balancing system robustness and efficiency.
Area of Science:
- Cellular Biology
- Physiology
- Biophysics
Background:
- Nutrient homeostasis is crucial for organism survival, maintaining stable internal nutrient levels despite external fluctuations.
- Transcriptional regulation of plasma membrane transporters is traditionally viewed as the primary mechanism for achieving nutrient homeostasis.
Purpose of the Study:
- To investigate the limitations of transcriptional regulation in achieving global perfect nutrient homeostasis.
- To identify and evaluate alternative mechanisms, such as activity-dependent regulation, for achieving robust nutrient homeostasis.
Main Methods:
- Mathematical modeling to analyze the criteria for global perfect homeostasis.
- Simulation of transporter regulation mechanisms, including activity-dependent downregulation and synthesis regulation.
Main Results:
- Transcriptional regulation alone does not achieve global perfect homeostasis, where internal nutrient levels are independent of external concentrations.
- Activity-dependent transporter downregulation meets the criterion for global perfect homeostasis by inversely relating transporter levels to net nutrient flux.
- Combining activity-dependent regulation with internal nutrient level sensing offers a more robust and efficient homeostatic system.
Conclusions:
- Activity-dependent transporter regulation is a critical, biologically plausible mechanism for achieving nutrient homeostasis.
- A hybrid regulatory system combining activity-dependent and internal-level-dependent mechanisms can overcome individual limitations.
- Re-evaluation of regulatory mechanisms in other homeostatic systems is warranted, considering the utility of activity-dependent regulation.
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