Structure, Dynamics, and Transport in Mitochondrial Networks

Mitochondria form network architectures ranging from partially fragmented to highly fused, depending on metabolic state and expression of fusion/fission proteins. Using spatially-resolved, agent-based simulations and mean-field models, we establish how experimentally tractable parameters such as local fusion/fission kinetics and mitochondrial mechanics and mobility shape network structure. We demonstrate that increased mitochondrial motion and junction flexibility inhibit the onset of a percolation transition in network connectivity. Distinct mammalian and yeast network structures are shown to arise from similar microscopic rate constants as a result of different geometric constraints. The intermediate fusion regime observed in mammalian cells is also shown to optimize rapid network rearrangement. We further employ our model to explore biomolecular spread through a mitochondrial population. In budding yeast, we highlight a potential mechanism for cellular aging in which selective mitochondrial transport and protein import lead to asymmetric content distribution between mother and daughter cells. In patterned mammalian cells, our model illustrates how the sparse transport events needed to maintain a broad mitochondrial mass distribution propel asymmetric spread of mitochondrial material.