Markov Modelling of Mitochondrial BAK Activation Kinetics during Apoptosis

  • C. Grills
  • D. A. Fennell
  • S. F. C. Shearer
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5792)


The molecular mechanism underlying mitochondrial BAK activation during apoptosis remains highly controversial. Two seemingly conflicting models known as the agonism model and the de-repressor model have been proposed. In the agonism model, BAK requires activator BH3 only proteins to initiate a series of events that results in cell apoptosis. In the de-repressor model the antagonism of pro-survival BCL-2 family proteins alone is sufficient for BAK activation kinetics to promote apoptosis. To gain a better understanding of the kinetic implications of these models and reconcile these opposing, but highly evidence-based theories, we have formulated Markov chain models which capture the molecular mechanisms underlying both the agonism and de-repressor models. Our results indicate that both pure agonism and dissociation are mutually exclusive mechanisms capable of initiating mitochondrial apoptosis by BAK activation.


BAK activation kinetics apoptosis BH3-only proteins BCL-2 family proteins agonism model derepressor model 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • C. Grills
    • 1
  • D. A. Fennell
    • 1
  • S. F. C. Shearer
    • 1
  1. 1.Centre for Cancer Research and Cell BiologyQueen’s UniversityBelfastN. Ireland

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