Autophagy pp 173-188 | Cite as

Formation of Autophagosomes Coincides with Relaxation of Membrane Curvature

  • Jaime Agudo-Canalejo
  • Roland L. KnorrEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1880)


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 modeling 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 pre-autophagosomal membranes such as vesicles, membrane tubules, or sheets. We analyze 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.

Key words

Reverse autophagy Membrane remodeling Fusion Scission Bending energy Membrane curvature Theory modeling Retrograde autophagy 



We thank Reinhard Lipowsky (MPI of Colloids and Interfaces) for stimulating discussions and institutional and financial support.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Rudolf Peierls Centre for Theoretical PhysicsUniversity of OxfordOxfordUK
  2. 2.Department of ChemistryThe Pennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of Theory and Bio-SystemsMax Planck Institute of Colloids and InterfacesPotsdamGermany
  4. 4.Department of Biochemistry and Molecular Biology, Graduate School and Faculty of MedicineThe University of TokyoTokyoJapan

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