Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis

Seongho Ryu, Shih Chieh Lin, Nadia Ugel, Marco Antoniotti, Bhubaneswar Mishra

Research output: Contribution to journalArticle

Abstract

Caspase-9 is the protease that mediates the intrinsic pathway of apoptosis, a type of cell death. Activation of caspase-9 is a multi-step process that requires dATP or ATP and involves at least two proteins, cytochrome c and Apaf-1. In this study, we mathematically model caspase-9 activation by using a system of ordinary differential equations (an ODE model) generated by a systems biology tool Simpathica-a simulation and reasoning system, developed to study biological pathways. A rudimentary version of ''model checking'' based on comparing simulation data with that obtained from a recombinant system of caspase-9 activation, provided several new insights into regulation of this protease. The model predicts that the activation begins with binding of dATP to Apaf-1, which initiates the interaction between Apaf-1 and cytochrome c, thus forming a complex that oligomerizes into an active caspase-9 holoenzyme via a linear binding model with cooperative interaction rather than through network formation.

Original languageEnglish (US)
Pages (from-to)49-66
Number of pages18
JournalSystems and Synthetic Biology
Volume2
Issue number1-2
DOIs
StatePublished - Jun 2008

Fingerprint

Apoptosomes
Caspase 9
Cell death
Chemical activation
Apoptosis
Cytochromes c1
Proteins
Peptide Hydrolases
Adenosinetriphosphate
Model checking
Holoenzymes
Ordinary differential equations
Systems Biology
Cytochromes c
Linear Models
Cell Death
Adenosine Triphosphate

Keywords

  • Apoptosis
  • Apoptosome
  • Caspase-9 ODE model
  • Computational systems biology
  • Model checking
  • Model comparison and selection

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Molecular Biology

Cite this

Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis. / Ryu, Seongho; Lin, Shih Chieh; Ugel, Nadia; Antoniotti, Marco; Mishra, Bhubaneswar.

In: Systems and Synthetic Biology, Vol. 2, No. 1-2, 06.2008, p. 49-66.

Research output: Contribution to journalArticle

Ryu, Seongho ; Lin, Shih Chieh ; Ugel, Nadia ; Antoniotti, Marco ; Mishra, Bhubaneswar. / Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis. In: Systems and Synthetic Biology. 2008 ; Vol. 2, No. 1-2. pp. 49-66.
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