Transport and Mixing through Dynamic Mitochondrial Networks

Mitochondria form dynamically interconnected networks responsible for supplying the energetic needs of eukaryotic cells, as well as participating in various cellular signaling pathways. Mitochondrial architectures  range from `social networks' of transiently interacting fragments to percolated physical networks of connected tubules. The mixing of mitochondrial contents, involved in quality control, sorting, and delivery to subcellular regions, is governed by the temporal and spatial connectivity of these networks.

We use a combination of mean-field continuum models and agent-based stochastic simulations to explore material spreading in mitochondrial networks. A simplified analytic model bridges between two limiting regimes:  a social network of diffusing particles that encounter each other in three-dimensional space, and hyperfused stationary networks that form lower-dimensional fractal-like structures. Analysis of mitochondrial architectures in several mammalian cell types indicates that they span across multiple regimes, implying that cells can tune network structure to obtain distinct transport properties. Our modeling approach predicts the time-scales for locally produced proteins to penetrate throughout the mitochondrial population, and these results are compared against experimental measurements of photoconverted protein spreading in mammalian mitochondria. By integrating modeling with analysis of live-cell imaging data from collaborating groups, we elucidate how the interplay of transport, fusion -- fission dynamics, and liquid-like structural rearragements govern heterogeneity within mitochondrial networks.