Int. J. Mol. Sci. 2010, 11(3), 982-1019; doi:10.3390/ijms11030982
Review

Application of the Principles of Systems Biology and Wiener's Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo

1email and 1,2,* email
Received: 30 January 2010; in revised form: 26 February 2010 / Accepted: 26 February 2010 / Published: 8 March 2010
(This article belongs to the Special Issue Quantitative Modelling in Molecular System Bioenergetics)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener’s cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener’s cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures – intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of cytosolic ADP, Pi and Cr/PCr ensures metabolic stability necessary for normal function of cardiac cells.
Keywords: muscle cells; respiration; regulation; metabolic homeostasis; mitochondria; §cytoskeleton; systems biology; phosphotransfer networks
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MDPI and ACS Style

Guzun, R.; Saks, V. Application of the Principles of Systems Biology and Wiener's Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo. Int. J. Mol. Sci. 2010, 11, 982-1019.

AMA Style

Guzun R, Saks V. Application of the Principles of Systems Biology and Wiener's Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo. International Journal of Molecular Sciences. 2010; 11(3):982-1019.

Chicago/Turabian Style

Guzun, Rita; Saks, Valdur. 2010. "Application of the Principles of Systems Biology and Wiener's Cybernetics for Analysis of Regulation of Energy Fluxes in Muscle Cells in Vivo." Int. J. Mol. Sci. 11, no. 3: 982-1019.

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