Dynamics of Mitochondrial Redox and Energy Networks: Insights from an Experimental–Computational Synergy - Systems Biology of Metabolic and Signaling Networks - page 138

loops. When applied systematically and rigorously the synergetic loop
of experiment-model enables a deeper understanding of complex biological
phenomena as shown in this chapter. Thorough application of this strategy both
enabled us to formulate the following new concepts and to unravel complex
emergent phenomena exhibited by networks of metabolic and electromechanical
processes in the cardiac cell:
￿ Mitochondria are organized as a dynamic network of oscillators in the cardiac
myocyte
￿ The mitochondrial network is synchronized by ROS to different degrees of
coupling strength, either weakly or strongly during physiological or pathophysi-
ological behavior, respectively.
￿ The mitochondrial network is embedded within other metabolic networks of the
cardiac cell, thereby interacting with metabolic, electrical, and mechanical
processes.
￿ Emergent phenomena take place in these networks in the form of physiologically
normal long-term correlations involving signaling processes, or as failures that
can propagate from the subcellular to the whole heart producing potentially
catastrophic arrhythmias (see Chap. 10 ).
￿ Striking similarities between the cardiac redox control systems and those in the
evolutionarily distant organism, baker's yeast ( Saccharomyces cerevisiae ), indi-
cate an ancient commonality of central core metabolic mechanisms (see
Chap. 12 ) , and how a mutually enhanced understanding of these can be gleaned
from comparative studies of different biological systems (Aon et al. 2007c ,
2008b ; Lemar et al. 2007 ; Lloyd et al. 2012 ).
Acknowledgments This work was performed with the financial support of R21HL106054 and
R01-HL091923 from NIH.
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