Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/42660
Title: Multistationary and oscillatory modes of free radicals generation by the mitochondrial respiratory chain revealed by a bifurcation analysis.
Author: Selivanov, Vitaly A.
Cascante i Serratosa, Marta
Friedman, M.
Schumaker, M. F.
Trucco, Massimo
Votyakova, Tatyana V.
Keywords: Reaccions de radicals lliures
Mitocondris
Free radical reactions
Mitochondria
Issue Date: 2012
Publisher: Public Library of Science (PLoS)
Abstract: The mitochondrial electron transport chain transforms energy satisfying cellular demand and generates reactive oxygen species (ROS) that act as metabolic signals or destructive factors. Therefore, knowledge of the possible modes and bifurcations of electron transport that affect ROS signaling provides insight into the interrelationship of mitochondrial respiration with cellular metabolism. Here, a bifurcation analysis of a sequence of the electron transport chain models of increasing complexity was used to analyze the contribution of individual components to the modes of respiratory chain behavior. Our algorithm constructed models as large systems of ordinary differential equations describing the time evolution of the distribution of redox states of the respiratory complexes. The most complete model of the respiratory chain and linked metabolic reactions predicted that condensed mitochondria produce more ROS at low succinate concentration and less ROS at high succinate levels than swelled mitochondria. This prediction was validated by measuring ROS production under various swelling conditions. A numerical bifurcation analysis revealed qualitatively different types of multistationary behavior and sustained oscillations in the parameter space near a region that was previously found to describe the behavior of isolated mitochondria. The oscillations in transmembrane potential and ROS generation, observed in living cells were reproduced in the model that includes interaction of respiratory complexes with the reactions of TCA cycle. Whereas multistationarity is an internal characteristic of the respiratory chain, the functional link of respiration with central metabolism creates oscillations, which can be understood as a means of auto-regulation of cell metabolism.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pcbi.1002700
It is part of: PLoS Computational Biology, 2012, vol. 8, num. 9, p. e1002700
Related resource: http://dx.doi.org/10.1371/journal.pcbi.1002700
URI: http://hdl.handle.net/2445/42660
ISSN: 1553-734X
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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