Mitochondrial network branching enables rapid protein spread with slower mitochondrial dynamics

Abstract

Mitochondrial network structure is controlled by the dynamical processes of fusion and fission, which merge and split mitochondrial tubes into structures including branches and loops. To investigate the impact of mitochondrial network dynamics and structure on the spread of proteins and other molecules through mitochondrial networks, we used stochastic simulations of two distinct quantitative models that each included mitochondrial fusion and fission, and particle diffusion via the network. Better-connected mitochondrial networks and networks with faster dynamics exhibit more rapid particle spread on the network, with little further improvement once a network has become well-connected. As fragmented networks gradually become better-connected, particle spread either steadily improves until the networks become well-connected for slow-diffusing particles or plateaus for fast-diffusing particles. We compared model mitochondrial networks with both end-to-end and end-to-side fusion, which form branches, to non-branching model networks that lack end-to-side fusion. To achieve the optimum (most rapid) spread that occurs on well-connected branching networks, non-branching networks require much faster fusion and fission dynamics. Thus the process of end-to-side fusion, which creates branches in mitochondrial networks, enables rapid spread of particles on the network with relatively slow fusion and fission dynamics. This modeling of protein spread on mitochondrial networks builds towards mechanistic understanding of how mitochondrial structure and dynamics regulate mitochondrial function.