Membrane fission via transmembrane contact

Division of intracellular organelles often correlates with additional membrane wrapping, e.g., by the endoplasmic reticulum or the outer mitochondrial membrane. Such wrapping plays a vital role in proteome and lipidome organization. However, how an extra membrane impacts the mechanics of the division has not been investigated. Here we combine fluorescence and cryo-electron microscopy experiments with self-consistent field theory to explore the stress-induced instabilities imposed by membrane wrapping in a simple double-membrane tubular system. We find that, at physiologically relevant conditions, the outer membrane facilitates an alternative pathway for the inner-tube fission through the formation of a transient contact (hemi-fusion) between both membranes. A detailed molecular theory of the fission pathways in the double membrane system reveals the topological complexity of the process, resulting both in leaky and leakless intermediates, with energies and topologies predicting physiological events.