Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation

Mitochondria maintain a constant rate of aerobic respiration over a wide range of oxygen levels. However, the control strategies underlying oxygen homeostasis are still unclear. Using mathematical modeling, we found that the mitochondrial electron transport chain (ETC) responds to oxygen level chang...

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Bibliographic Details
Published in:Biophysical journal 2013-03, Vol.104 (6), p.1338-1348
Main Authors: Kueh, Hao Yuan, Niethammer, Philipp, Mitchison, Timothy J.
Format: Article
Language:English
Subjects:
aerobiosis
Cell Respiration
Computational Biology
electron transfer
Electron Transport
electron transport chain
Homeostasis
Kinetics
Mathematical models
Mitochondria
Mitochondria - metabolism
Models, Biological
Oxygen
Oxygen - metabolism
Respiratory system
Systems Biophysics
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Summary:Mitochondria maintain a constant rate of aerobic respiration over a wide range of oxygen levels. However, the control strategies underlying oxygen homeostasis are still unclear. Using mathematical modeling, we found that the mitochondrial electron transport chain (ETC) responds to oxygen level changes by undergoing compensatory changes in reduced electron carrier levels. This emergent behavior, which we named cosubstrate compensation (CSC), enables the ETC to maintain homeostasis over a wide of oxygen levels. When performing CSC, our ETC models recapitulated a classic scaling relationship discovered by Chance [Chance B (1965) J. Gen. Physiol. 49:163-165] relating the extent of oxygen homeostasis to the kinetics of mitochondrial electron transport. Analysis of an in silico mitochondrial respiratory system further showed evidence that CSC constitutes the dominant control strategy for mitochondrial oxygen homeostasis during active respiration. Our findings indicate that CSC constitutes a robust control strategy for homeostasis and adaptation in cellular biochemical networks.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2013.01.030