Actin Cytoskeleton-Mediated Constriction of Membrane Organelles via Endoplasmic Reticulum Scaffolding.

Intracellular organelles constantly undergo fission to facilitate turnover, transport, and functional changes. The cytoskeleton has long been understood to play a role in these events, and recent work strongly suggests that several conserved molecular players cooperate with the cytoskeleton to mediate the fission process. Membrane curvature-inducing, membrane scission proteins, and force-inducing cytoskeletal proteins all cooperate to drive the fission process. Recent work suggests that the endoplasmic reticulum serves as the linchpin that orchestrates and spatially organizes fission via these curvature-inducing, scission, and force-producing molecules. This all leads us to postulate a "universal theory" of organelle fission with distinct biophysical and biochemical features mediated by a finite number of physical and molecular constraints. This new physical paradigm deserves special attention from those who wish to model these processes, since previous theoretical and experimental attempts to elucidate these fission mechanisms have not included the organizing factor of the endoplasmic reticulum. Here we review the basic concepts of this new model for organelle fission, and explore the implications thereof. Previous studies that didn't include this component can now be interpreted in light of these new data and serve as a useful guide for understanding how this process happens in vivo. Thus, this review provides direction for future modeling and experimental efforts to better understand how these complex systems and processes are regulated in both healthy and diseased biological systems.