Inducible intracellular membranes: molecular aspects and emerging applications

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).

The AAA+ ATPase RavA and its binding partner ViaA modulate E. coli aminoglycoside sensitivity through interaction with the inner membrane

“…4b ). One should keep in mind that as observed for some rare membrane proteins 30 , an inner membrane stress due to its saturation resulting from the ViaA overexpression may be relieved by induction of the CL-enriched neo-membranes that enclose the excess of ViaA. At physiological concentrations of ViaA however, the CL content of the inner membrane may not be significantly higher than in the absence of ViaA, and a massive membrane tubulation as observed in Fig.…”

“…3b ). Interestingly, overexpression of few membrane proteins with particular topologies has previously been noticed to induce formation of tubular membrane networks of reminiscent hexagonal phase morphologies 28 – 30 . Such cardiolipin (CL)-enriched neo-membranes are proposed to form in order to accommodate the highly overproduced membrane protein, thereby relieving the inner cellular membrane from the associated stress.…”

“…Consequently, the association of ViaA-OE with PA at the inner membrane level could trap PA, thereby preventing Cls inhibition and eventually favouring CL synthesis, leading to a modification in the lipid homeostasis. Independently of the concrete mechanism and considering the physiologically low amount of ViaA inside the E. coli cell, one may anticipate that by binding to cone-shaped anionic phospholipids such as PA and CL, natively expressed ViaA may locally act on the inner membrane curvature, affect its permeability or influence some other local membrane properties 30 .…”

Formation of intracellular vesicles within the Gram+ Lactococcus lactis induced by the overexpression of Caveolin-1β

“…The production by L. lactis of numerous internal dense caveolar vesicles enriched of various endogenous MP normally resident in the plasma membrane indicates that caveolin-1β biosynthesis occurs, at the level of the plasma membrane, in functional domains that appear to be shared with the bulk biosynthesis of the whole MPs of the bacterial host. Such domains, similar to the so-called transertion domains described for E. coli and Bacillus subtilis, that allow concerted transcription, translation and membrane insertion of neo-synthesized MPs [54], have been recognized to play a pivotal role for the appearance of various ectopic intracellular membrane structures induced by overexpression of some MPs in bacteria [49]. Indeed, these domains allow the recruitment in the close membrane vicinity of the neo-synthesized caveolin-1β of various MPs before vesiculation occurs.…”

Mitochondrial Membrane Remodeling

“…Genetic deletion of the PSD enzyme leads to swollen, rounded, and fragmented mitochondria, indicating that PE is critical for mitochondrial morphology ( Steenbergen et al, 2005 ). Several excellent reviews summarize our current understanding of lipid signaling and its scaffolding role ( Tatsuta et al, 2014 ; Aufschnaiter et al, 2017 ; Dudek, 2017 ; Nielson and Rutter, 2018 ; Royes et al, 2020 ).…”