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Int. J. Mol. Sci. 2009, 10(2), 702-722; doi:10.3390/ijms10020702
Review

A Systems Biology Approach to Investigating Apoptotic Stimuli as Effectors of Cell Metabolism: Practical Application of Top-Down Control Analysis to Attached Neurons

Received: 20 January 2009; in revised form: 19 February 2009 / Accepted: 19 February 2009 / Published: 23 February 2009
(This article belongs to the Special Issue Molecular System Bioenergetics)
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Abstract: Reduced glycolytic and mitochondrial respiration rates are common features of apoptosis that may reflect key events contributing to cell death. However, it is unclear to what extent the rate changes can be explained by direct alterations in the kinetics of the participating reactions, as changes in the concentrations of intermediates also affect reaction rates. Direct kinetic changes can be identified, ranked, and compared to the indirect effects mediated by the intermediates using top-down control analysis. Flux changes that are explained primarily by direct effects are likely to be prime targets of the pathways that signal death, and thus important contributors to apoptosis. Control analysis concepts relevant to identifying such effects are reviewed. Metabolic flux measurements are essential for this approach, but can be technically difficult, particularly when using adherent cells such as neurons. A simple method is described that renders such measurements feasible.
Keywords: Apoptosis; glycolysis; mitochondria Apoptosis; glycolysis; mitochondria
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.

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MDPI and ACS Style

Jekabsons, M.B. A Systems Biology Approach to Investigating Apoptotic Stimuli as Effectors of Cell Metabolism: Practical Application of Top-Down Control Analysis to Attached Neurons. Int. J. Mol. Sci. 2009, 10, 702-722.

AMA Style

Jekabsons MB. A Systems Biology Approach to Investigating Apoptotic Stimuli as Effectors of Cell Metabolism: Practical Application of Top-Down Control Analysis to Attached Neurons. International Journal of Molecular Sciences. 2009; 10(2):702-722.

Chicago/Turabian Style

Jekabsons, Mika B. 2009. "A Systems Biology Approach to Investigating Apoptotic Stimuli as Effectors of Cell Metabolism: Practical Application of Top-Down Control Analysis to Attached Neurons." Int. J. Mol. Sci. 10, no. 2: 702-722.


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