An agent-based model of mitochondrial dynamics determined by organelle mobility and fusion-fission cycles.

Abstract

<p>(A) Model representation. The model consists of a two-dimensional grid (elements of 1 μm × 1 μm) in which the cell is represented by a circle with a diameter of 50 μm, and a nucleus with a diameter of 16.6 μm. The dashed circle (diameter, 25 μm) divides the cell in two regions, perinuclear (red arrow) and cytosolic (blue arrow), with different mitochondrial mobility. The mitochondrial population consists of agents with masses ranging continuously from a minimum value M_min of 0.5 μm² to a maximum value Mmax of 3 μm². The mitochondria population is in turn subdivided into three groups: small (mass smaller or equal 1 μm², orange), medium (mass between 1 μm² and 2 μm², blue) and large (mass greater than 2 μm², green). (B) Schematic describing mitochondrial dynamics, consisting of fusion (<i>f</i>) and fission (<i>F</i>) cycles occurring with temporal frequencies (f_f, F_f) of minutes. Mitochondria of all masses are able to undergo fusion and fission events according to fusion and fission probabilities (f_p, F_p). Time step used in all the simulation, Δt = 1sec. (C) Schematic describing mitochondrial movement and unfeasible actions. Each mitochondrion checks, with an internal control, the surrounding area with a radius of 1.0 μm in order to avoid unfeasible actions such as moving outside the cell or inside the nucleus and overlapping other mitochondria. If the area is free, the mitochondrion first move one step forward, with a velocity <i>v</i>, and than rotates by a random angle ϑ₁ ϵ [0°, 360°]. If the mitochondrion encounters either another mitochondrion (and no fusion occur), the nucleus, or the cell border, the mitochondrion rotates by a random angle ϑ₂ ϵ[0°, 90°]. (D) Basic flow chart of the model representing the fusion-fission cycle and main components of the model. Shaded boxes indicate the main processes of the model (fusion and fission) with the respective governing equations.</p