Dynamics of Mitochondrial Redox and Energy Networks: Insights from an Experimental–Computational Synergy - Systems Biology of Metabolic and Signaling Networks - page 111

Chapter 5
Dynamics of Mitochondrial Redox and
Energy Networks: Insights from an
Experimental-Computational Synergy
Sonia Cortassa and Miguel A. Aon
Abstract Functionally, a cell comprises spatially distributed and compartment-
alized subsystems, the dynamics of which occurs on several temporal scales.
Interactivity in complex spatiotemporally organized cellular systems is funda-
mental to their counterintuitive behavior and one of the main reasons why their
study needs mathematical modeling. But models alone are not enough; what we
ultimately require is a combined experimental-theoretical approach in order to
validate our models as rigorously as possible.
We explore in a detailed example the success of experimental-modeling synergy
leading to the elucidation of the mechanisms involved in synchronized mitochon-
drial oscillations in the heart, and the discovery there of new related mechanisms.
This work involves successive and iterative reciprocal potentiation of the loop via
experiments and computational modeling: simulation-validation and prediction-
experimentation thereby alternate so as to provide a deeper understanding of
complex biological phenomena.
The concept of network has become central in systems biology. Conceptually,
networks can be approached from different angles. One is morphological ,in
which mitochondrial spatial organization corresponds to a network because they
exhibit a spatial arrangement with a defined pattern that topologically connects
them in a certain way, for example, in a lattice as in cardiac cells, or reticular
random as in neurons or cancer cells. However, underlying these networks there is
another vast network of metabolic reactions with nodes represented by substrates,
products, ion gradients, and links by enzymes catalyzing reactions between
substrates and products, or transporters and channels modulating the passage of
ions and metabolites across membranes. The metabolic network distributes among
S. Cortassa ￿ M.A. Aon ( * )
Division of Cardiology, Johns Hopkins University, Baltimore, MD 21205, USA
e-mail: [e-mail]