Structural Biochemistry/Membrane Fission

Introduction
Membrane fission is the process in which a cellular membrane that is initially incessant is split into two distinct membranes. This activity is important in normal processes such as exocytosis and cellular reproduction and is used to separate and transport molecules from organelles with a cell to the lipid bilayer and vice versa. Membrane fission is also the direct opposite of membrane fusion and has separate proteins that will facilitate its process.

Pre-Requisites
To make a separate membrane-bound subunit without changing the original bilayer, the lipid bilayer needs to be changed and distorted locally. This must be done without creating any leakages of the carrier’s insides, thus, a fission pathway with the formation of a hemifission state is required. This hemifission state involves forming a narrow neck pathway, merging the monolayers as an intermediate, and decaying the intermediate to complete the fission reaction. The entire formation requires bending, tilting, or curving of the bilayer.

The changing of position of the lipids lead to elastic stresses, storing elastic energy in the bilayer. An outside force is needed in order to stretch, compress, tilt or bend a piece of membrane. For membrane fission to happen energetically, the total free energy (external energy plus internal energy) needs to be lower after the fission process finishes.

Process and Proteins Involved
Membrane fission begins when a cellular membrane that is initially continuous begins to form a membrane neck. This neck is similar to a fusion pore and decreases in width until it fully deteriorated and the resulting two membranes form. Energy to distort the membrane and form the membrane neck is provided by the GTPase Dynamin.

The formation of the membrane neck is related to the creation of protein coats (membrane scaffolding) performed by protein complexes. The formation of protein coats can eventually lead to a membrane neck which is then narrowed by the constant construction of these protein coats. Proteins that are involved in this include CHMP2 and CHMP3 which are both charged multivesiclar body proteins. The formation of the membrane neck can also be facilitated by the insertion of hydrophobic and amphipathic proteins into or next to the cell membrane. Examples of these proteins include the BAR-domain and Dynamin family proteins which are placed onto the cell membrane.

ESCRT-III can catalyze membrane fission similarly to Dynamin family proteins except it assemblies inside the membrane which causes it to tighten and eventually start a fission. This protein is not only important for cell membrane fission, but also cytokinesis suggesting the relationship between cell membrane fission and cell reproduction.

Similarity and Differences from Membrane Fusion
Membrane fission shares many similarities to membrane fusion as it is the opposite process, but also has some unique features. Both will lead to the formation of a pore like structure with a membrane neck. However for fusion, this neck will expand and eventually align linearly while for fission the neck will narrow until it is fully degraded and form two membranes are more bent in nature. The reasoning for the difference in alignment is that for fusion, the end result is a longer piece of membrane while for fission the result is two shorter pieces of membrane from the starting one.

Forces that favor membrane fission will inhibit membrane fusion while the opposite will occur for forces that inhibit it. Forces that will promote membrane bending will encourage membrane fission. This is due to the increased ability for the membrane to form the membrane neck structure created in membrane fission. Forces that decrease the membrane fluidity will have the opposite effect and as a side effect, promote membrane fusion. The membrane will not be able to form the neck used for fission as readily but the neck used for fusion in which another membrane attaches to the structure and eventually straightens out.

Dynamin family proteins, which are highly involved in several membrane fission initiations as noted, are also involved in some membrane fissions initiations. An example is in the mitochondrial cell membrane in which the Dynamin family proteins restructure the membrane by starting fission and fusion processes. For this, Dnm1 and Drp1 are the main Dynamin family proteins involved in fission while Fzo1 and Mgm1 are involved in fusion.