Modification of membrane lipid compositions in single-celled organisms – From basics to applications

Abstract

All intact cells, and their organelles, are surrounded by a ∼30 Å hydrophobic film that typically separates the interior from the environment. This film is composed of lipid bilayers that form from a pool of structurally highly diverse, amphipathic lipids. The specific composition and nature of these lipids strongly contributes to many different processes in the cell by influencing membrane structures, membrane protein sorting and functionalities. In this review, we discuss strategies to alter membrane lipid compositions of organelles and plasma membranes in different organisms, focusing on microbial cells. Reflecting the many essential roles of lipids in cellular regulation, we delineate diverse cellular processes affected by membrane lipid modifications and discuss possible applications in a biotechnological and biomedical context. A major motivation for membrane lipid engineering has been the improvement of expression, translocation and activity of heterologous membrane proteins, which can facilitate the biochemical and structural characterization of this challenging class of proteins. Additionally, better expression of membrane proteins or membrane lipid engineering - or a combination of both - led to improved production of high-value compounds and food additives, e.g. polyunsaturated fatty acids and glycolipids, in diverse hosts. More recently it has been shown that diverse cellular pathologies such as cancer and Alzheimer's disease are associated with lipid alterations. Hence, the progress in our understanding of membrane structure, function and protein-lipid interactions, and the resulting possibilities regarding the engineering of membrane lipid composition clearly enable novel nutraceutical and pharmaceutical interventions to be developed. Significant progress in this important area of research is highlighted in this review.

Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches

“…Most membrane lipids pass at some point the Golgi apparatus. The Golgi is a centre for membrane lipid modification and further trafficking, and in this context is especially important for the synthesis and glycosylation of sphingolipids [ 9 , 13 , 14 ]. Membrane lipids are eventually trafficked to the plasma and organellar membranes.…”

IntEResting structures: formation and applications of organized smooth endoplasmic reticulum in plant cells

“…This could lead to an accumulation of proteins in the ER, which if dimerizing and membrane-resident could trigger the formation of OSER, via mechanisms consistent with either the "threshold model" or the "membrane proliferation model". As ER stress is usually also associated with ER membrane proliferation activated by the unfolded protein response (UPR) (Pichler and Emmerstorfer-Augustin, 2018), an alternative possibility is that the "export inhibition pathway" feeds directly into the "membrane proliferation model" for OSER formation. The fact that when overexpressing OSER inducing proteins, ER-to-Golgi export is not usually disrupted (as seen by the correct localisation of exported markers (Yamamoto et al, 1996)) suggests that ER export inhibition is sufficient, but not necessary for OSER formation.…”

“…Moreover, as Eukaryotes, plants have an innate capacity for the proper folding of proteins with secondary (or more complex) structures and addition of post-translational modifications. There is growing interest in the bioproduction of commercially valuable membrane-bound proteins (Pedrazzini, 2009;Pichler and Emmerstorfer-Augustin, 2018). These are often difficult to express, and since the ratio of proteins-to-lipids in biological membranes could be as high as 1:1, one bottleneck to membrane protein production was suggested to be the amount of membrane available to accommodate these (Pichler and Emmerstorfer-Augustin, 2018).…”

Intracellular Membranes: Conserved Mechanisms of Formation and Regulation Throughout Evolution

“…Historically, genetically modified strains have been developed to enhance membrane protein production (Miroux and Walker 1996;Baumgarten et al 2017;Angius et al 2018). Recently, a novel strategy has arisen for membrane protein production both in prokaryotes and eukaryotes, relying on tuning the cell membrane phospholipid composition to accommodate higher amounts of recombinant membrane proteins (Pichler and Emmerstorfer-Augustin 2018;Kanonenberg et al 2019). Some of the proteins triggering internal membrane proliferation, like the P9 protein of phage φ6, have been proposed as a fusion partner to membrane proteins to trigger membrane expansion and increase the yield of membrane protein production (Jung, Jung and Lim 2015).…”