Type

Journal Article

Authors

Markus Rehm
M Eugenia Delgado
Maximilian L Würstle
Selma F Jacob

Subjects

Biology

Topics
embryonic development spatial analysis experimental data reactive oxygen species programmed cell death theoretical framework mathematical models signal transduction

An Analysis of the truncated Bid- and ROS-dependent Spatial Propagation of Mitochondrial Permeabilization Waves during Apoptosis. (2015)

Abstract Apoptosis is a form of programmed cell death that is essential for the efficient elimination of surplus, damaged and transformed cells during metazoan embryonic development and adult tissue homeostasis. Situated at the interface of apoptosis initiation and execution, mitochondrial outer membrane permeabilization (MOMP) represents one of the most fundamental processes during apoptosis signal transduction. It was shown that MOMP can spatiotemporally propagate through cells, in particular in response to extrinsic apoptosis induction. Based on apparently contradictory experimental evidence, two distinct molecular mechanisms have been proposed to underlie the propagation of MOMP signals, namely a reaction-diffusion mechanism governed by anisotropies in the production of the MOMP-inducer truncated Bid (tBid), or a process that drives the spatial propagation of MOMP by sequential bursts of reactive oxygen species (ROS). We therefore generated mathematical models for both scenarios and performed in silico simulations of spatiotemporal MOMP signalling in order to identify which one of the two mechanisms is capable of qualitatively and quantitatively reproducing the existing data. We found that the explanatory power of each model was limited in that only a subset of experimental findings could be replicated. However, the integration of both models into a combined mathematical description of spatiotemporal tBid and ROS signalling accurately reproduced all available experimental data and furthermore provided robustness to spatial MOMP propagation when mitochondria are spatially separated. Our study therefore provides a theoretical framework that is sufficient to describe and mechanistically explain the spatiotemporal propagation of one of the most fundamental processes during apoptotic cell death.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Markus Rehm, M Eugenia Delgado, Maximilian L Würstle, Selma F Jacob

Experts in our system

1
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55
 
2
Maximilian L Würstle
Royal College of Surgeons in Ireland
Total Publications: 13