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Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation

Authors
Journal
Biophysical Journal
0006-3495
Publisher
Elsevier
Publication Date
Volume
104
Issue
6
Identifiers
DOI: 10.1016/j.bpj.2013.01.030
Keywords
  • Systems Biophysics
Disciplines
  • Chemistry
  • Mathematics
  • Medicine

Abstract

Abstract 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.

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