BPS2026 – Diffusive spreading on dynamic, solid, and liquid mitochondrial networks

Mitochondria are dynamic organelles, forming a plethora of unique network structures through fusion, fission, transport, and rearrangement. Using a spatially resolved modeling framework, we explore the emergence of different network structures from local interactions and uncover the relationship between diffusive spreading rates and mitochondrial structure and dynamics. Material spreading from localized sources—such as calcium from ER contact sites or labeled proteins from photoconverted regions—is analyzed across diverse network architectures. In hyperfused networks, dispersion depends on diffusion along tubules and is well-described by a fractal continuum approach. In fragmented networks, encounters driven by mitochondrial mobility and fusion allow for spreading through the three-dimensional population. A less-appreciated aspect of mitochondrial dynamics is liquid-like topological rearrangements. We model the effect of sliding and branching on mitochondrial network structure, highlighting the differences in topological features like the number of loops when junctions are formed via branching vs. tip-side fusion. We also examine the effect of these liquid-like rearrangements on the transport of diffusive material through the network. Our theoretical results are used to predict the rate of photoconverted protein spreading across mitochondrial architectures in different cell types, demonstrating how these networks can span from the hyperconnected to the partly fragmented regime. Analytic predictions are further corroborated by explicit voxel-voxel diffusion simulations run on fast-framerate movies of mitochondrial networks. Overall, our modeling approach links mitochondrial structure and dynamics to transport, offering qualitative understanding and quantitative predictions for diffusive transport on dynamic networks.