Spreading Through Dynamic Mitochondrial Networks

In order to supply the energetic needs of eukaryotic cells, mitochondria are broadly distributed throughout the cell interior. The ability of mitochondria to fuse and exchange proteins and ions has been implicated in a variety of functionally important processes, including homeostatic maintenance, quality control, sorting, and signaling. Depending on cell type and metabolic conditions, the mitochondrial population varies from `social networks' of individual units that undergo transient interactions to extensive tubular networks that percolate throughout the cytoplasm. Starting with a framework of coarse-grained spatially resolved simulations of emergent mitochondrial networks, we explore how network structure and dynamics modulate the rate of spread of intra-mitochondrial contents through the population.

We show that spreading material transitions between two different regimes, with spatial propagation through network clusters over short timescales and social exchange between clusters at longer times. The exchange rates are governed by local fusion and fission, as well as cellular-scale mobility of mitochondrial clusters. For dendritic mitochondrial populations we demonstrate that mixing rates are determined primarily by the overall turnover time of the mitochondrial population as well as the stopping frequency during processive motion. In bulk mammalian cells, we find that the ability of mitochondria to acquire calcium from localized contact sites is aided by network connectivity, and that the physiologically observed network structures are sufficiently connected to yield near-maximal performance. Overall these results shed light on the interplay between mitochondrial transport, network structure, and diffusive mixing within the mitochondrial population.