  Autophagy is an intracellular degradation process that employs complex
membrane dynamics to isolate and break down cellular components. However, many
unanswered questions remain concerning remodeling of autophagic membranes.
Here, we focus on the advantages of theoretical modelling to study the
formation of autophagosomes and to understand the origin of autophagosomal
membranes. Starting from the well-defined geometry of final autophagosomes we
ask the question of how these organelles can be formed by combining various
preautophagosomal membranes such as vesicles, membrane tubules or sheets. We
analyse the geometric constraints of autophagosome formation by taking the area
of the precursor membranes and their internal volume into account. Our results
suggest that vesicle fusion contributes little to the formation of
autophagosomes. In the second part we quantify the curvature of the precursors
and report that the formation of autophagosomes is associated with a strong
relaxation of membrane curvature energy. This effect we find for a wide range
of membrane asymmetries. It is especially strong for small distances between
both autophagosomal membranes, as observed in vivo. We quantify the membrane
bending energies of all precursors by considering membrane asymmetries. We
propose that the generation and supply of pre-autophagosomal membranes is one
limiting step for autophagosome formation.
