Impact of Mitochondrial Dynamics on Diffusive Spread of Proteins

Mitochondria form dynamic networks and maintain their morphology via fission and fusion events. By adjusting the fission and fusion levels, mitochondria can modify their network structure. The role of mitochondria varies depending on cell types and conditions, which can manifest as variations in mitochondrial connectivity. To meet cellular demands, proteins can be exchanged within the linked mitochondrial network. To explore how protein spread is controlled by mitochondrial dynamics, we developed quantitative models of mitochondrial fission and fusion dynamics and protein diffusion via the network. Using stochastic simulations, we explore how variation in fission and fusion impacts the protein diffusivity and search time in the mitochondrial network. We use both a lattice-based spatial model and an agent-based model to represent mitochondrial networks both with and without network branching. We find that with branching, increasing fusion causes a monotonic but non-linear rise in diffusivity, which reduces search time. However, greater fusion without branching calcifies mitochondria into small networks and leads to a peak diffusivity (minimum search time) at intermediate fusion levels. This suggests that the branching nature of mitochondrial networks is crucial for protein spread.