Abstract
Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).
Highlights
Biological membranes are complex, two-dimensional structured assemblies of phospholipids containing a high density of proteins and carbohydrates
Four important questions about inner membrane proliferation upon protein overproduction remain: (1) how can overproduced proteins induce the deformation of the inner membrane creating different morphologies; (2) what are the characteristics of the proteins triggering lipid biosynthesis and, inner membrane proliferation; (3) how are protein overproduction and de novo phospholipid biosynthesis coordinated; and (4) can we find regulatory mechanisms conserved across evolution explaining internal membrane proliferation in both prokaryotic and eukaryotic cells
This study strongly suggests that the mechanisms involved in membrane curvature induction and, as a consequence, the morphology observed upon protein overproduction, are predictable and determined by physical laws
Summary
Biological membranes are complex, two-dimensional structured assemblies of phospholipids containing a high density of proteins and carbohydrates. The exact mechanism by which FisB triggers membrane fusion is still unknown, the protein is able to induce lipid mixing in vitro, in a process depending on the specific interaction between its periplasmic domain and CL.
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