The structure of tubular organelle networks can accelerate diffusive transport and kinetics

Diffusion is an important, and often dominant, mode of transport for molecules inside cells. Many cell processes occur within specialized organelles with a variety of internal geometries, notably the tubular networks of the endoplasmic reticulum and mitochondria, which form a complex meshwork of loops spanning much of the cell. We describe how the structure of these tubular network organelles controls diffusive search times and kinetic rates, using both analytical calculation and computational simulation of diffusive first-passage times on organelle structures extracted from yeast and mammalian cells. We find that total network length alone is not a good predictor of search time. However, total length combined with the number of loops robustly determines search times. Strikingly, increasing the number of loops substantially accelerates diffusive search and reaction kinetics. Mitochondrial mutant networks deficient in fusion and fission have many fewer loops than wild-type networks. By comparing these two network types we show wild-type networks can nearly double diffusive reaction rates for sparse reactants, compared to mutant networks. Overall, we find that the looped structure of organelle networks can function to accelerate diffusive processes.