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

关键词: Apoptosis;    glycolysis;    mitochondria;   

DOI  :  10.3390/ijms10020702

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.