Dynamics & transport in 3D mitochondrial networks.

Abstract

In many eukaryotic cells, mitochondria undergo extensive fusion to form dynamic, 3-dimensional network structures. We use simulations and mathematical models to explore how the formation of such networks can aid mitochondrial function through improving transport and distribution of proteins and other biomolecules. Our graph-based 3D representation of the mitochondrial network highlights the relative importance of mechanical constraints, remodeling, and motility mechanisms in determining the morphology of the network. We observe that mechano-structural limitations cause observed fusion rates to deviate from those predicted by well-mixed non-spatial models. In particular, the measured steady-state fusion rate reaches a maximum value at intermediate values of our fusion parameter before decreasing at higher values. Measured fusion rates also reveal a distinction between two types of remodeling events: large-scale rearrangement in which nodes connect and disconnect to other nodes following spatiotemporal displacement, and local “breathing” events in which nodes undergo fission immediately followed by re-fusion. We find that there exists a percolation threshold in cluster size at intermediate fusion rate constants, which may give the cell switch-like control over the architecture and dynamics of its mitochondrial network. By modeling diffusion of biomolecules on our simulated networks, we show that the existence of this threshold plays a role in optimizing signal and material transport between mitochondria. We demonstrate that dynamic network remodeling controls mitochondrial structure, which in turn governs the transport and mixing of mitochondrial components.