Title: Modelling of the mitochondrial apoptosis network

Authors: J. Cui, C. Chen, H. Lu, P. Shen

Addresses: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. ' State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. ' State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. ' State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China

Abstract: In this paper, we performed an experimental observation-based computer simulation of the regulatory network of mitochondrial apoptosis. By modelling we obtained dynamical understandings of various apoptosis-related proteins, including cytochrome c (cyt c) release and caspase activation. Through parameter analysis, we examined the role of Bcl-2 family proteins and the natural inhibitors of apoptosis in the regulatory network of apoptosis. Furthermore, the effects of several amplified loops in the network were found to enhance caspase activation and make the decision of apoptosis switch like. Consistent with most available experimental evidences, our results yield insights into the complex regulatory mechanism of mitochondrial apoptosis.

Keywords: mathematical modelling; mitochondrial apoptosis; Bcl-2 proteins; cyt c; IAP; caspase activation; bioinformatics; simulation; natural inhibitors; regulatory network; cytochrome c.

DOI: 10.1504/IJBRA.2008.018344

International Journal of Bioinformatics Research and Applications, 2008 Vol.4 No.2, pp.172 - 187

Available online: 17 May 2008 *

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