Autophagosome closure requires membrane scission

Abstract

During the intracellular process of macroautophagy (hereafter autophagy), a membrane-bound organelle, the autophagosome, is generated de novo. The remodeling of the autophagic membrane during the life cycle of the organelle is a complex multistep process and involves several changes in the topology of the autophagic membrane. Here, we focus on the final step of autophagosome formation, the closure of the phagophore, during which the inner and outer autophagic membranes become separate entities. We argue that this topological membrane transformation is a membrane scission event. Surprisingly, not a single recent review describes this substep as membrane scission (or membrane fission). In contrast, a number of publications imply that membrane fusion is involved. We discuss the potential sources for misinterpretation and recommend to consistent use of the unambiguous term "membrane scission."

Keywords: autophagy; closure; membrane fission; membrane fusion; membrane neck; membrane scission; nuclear pore; phagophore; sporulation; yeast.

Figure 1.

Membrane scission and membrane fusion. (A) Membrane scission (or fission) is illustrated for the case where 2 equally sized bilayers are formed from one bilayer. Fusion is the topologically reverse process, where 2 bilayers or vesicles merge into a single one. (B, C) The size and location of the 2 vesicles relative to each other are not relevant to identify a process as scission or fusion. (D) Membrane scission and fusion of 2 almost equally sized vesicles, stacked within each other. The formation of the autophagosome from the cup-shaped phagophore provides an example for a scission process. Each bilayer is depicted as a single line, solid lines represent directly “visible” bilayers and dashed lines correspond to bilayers evident in cross sections only.

Figure 2.

The scission neck. (A) The 2D cross-sectional views show 2 strongly bent membrane segments in the marked rectangular areas during autophagy (upper sketch) and endocytosis (lower sketch). (B) The rotated 3D view of the areas highlighted in (A) reveals that these 2 segments belong to a single scission neck.