Mathematical modelling of the mitochondrial apoptosis pathway

Mitochondria are pivotal for cellular bioenergetics, but are also a core component of the cell death machinery. Hypothesis-driven research approaches have greatly advanced our understanding of the role of mitochondria in cell death and cell survival, but traditionally focus on a single gene or specific signalling pathway at a time. Predictions originating from these approaches become limited when signalling pathways show increased complexity and invariably include redundancies, feedback loops, anisotropies or compartmentalisation. By introducing methods from theoretical chemistry, control theory, and biophysics, computational models have provided new quantitative insights into cell decision processes and have led to an increased understanding of the key regulatory principles of apoptosis. In this review, we describe the currently applied modelling approaches, discuss the suitability of different modelling techniques, and evaluate their contribution to the understanding of the mitochondrial apoptosis pathway. This article is part of a Special Issue entitled Mitochondria: the deadly organelle. (C) 2010 Elsevier B.V. All rights reserved.