Membrane Associated Complexes: New Approach to Calcium Dynamics Modelling

Mitochondria are one of the most important organelles determining Ca2+ regulatory pathway in the cell. Recent experiments suggested the existence of cytosolic microdomains with locally elevated calcium concentration (CMDs) in the nearest vicinity of the outer mitochondrial membrane (OMM). These intermediate physical connections between endoplasmic reticulum (ER) and mitochodria are called MAM (mitochondria-associated ER membrane) complexes. The aim of this paper is to take into account the direct calcium flow from ER to mitochondria implied by the existence of MAMs and perform detailed numerical analysis of the influence of this flow on the type and shape of calcium oscillations. Depending on the permeability of MAMs interface and ER channels, different patterns of oscillations appear (simple, bursting and chaotic). For some parameters the oscillatory pattern disappear and the system tends to a steady state with extremely high calcium level in mitochondria, which can be interpreted as a crucial point at the beginning of an apoptotic pathway.