Homeoviscous Adaptation and the Regulation of Membrane Lipids
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - PublisherReview Connector Homeoviscous Adaptation and the Regulation of Membrane Lipids Robert Ernst 1, Christer S. Ejsing 2 and Bruno Antonny 3 1 - Institute of Biochemistry and Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, 60438 Frankfurt, Germany 2 - Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, 5230 Odense, Denmark 3 - Institut de Pharmacologie Moléculaire et Cellulaire, Université Nice Sophia Antipolis and CNRS, 06560 Valbonne, France Correspondence to Robert Ernst and Christer S. Ejsing: [email protected]; [email protected] http://dx.doi.org/10.1016/j.jmb.2016.08.013 Edited by Ünal Coskun Abstract Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold. This adaptive response was termed homeoviscous adaptation and has been frequently studied with a specific focus on the acyl chain composition of membrane lipids. Mass spectrometry-based lipidomics can nowadays provide more comprehensive insights into the complexity of lipid remodeling during adaptive responses. Eukaryotic cells compartmentalize biochemical processes in organelles with characteristic surface properties, and the lipid composition of organelle membranes must be tightly controlled in order to maintain organelle function and identity during adaptive responses. Some highly differentiated cells such as neurons maintain unique lipid compositions with specific physicochemical properties. To date little is known about the sensory mechanisms regulating the acyl chain profile in such specialized cells or during adaptive responses. Here we summarize our current understanding of lipid metabolic networks with a specific focus on the role of physicochemical membrane properties for the regulation of the acyl chain profile during homeoviscous adaptation. By comparing the mechanisms of the bacterial membrane sensors with the prototypical eukaryotic lipid packing sensor Mga2 from Saccharomyces cerevisiae, we identify common operational principles that might guide our search for novel membrane sensors in different organelles, organisms, and highly specialized cells. © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction receptors, transporters, enzymes, and structural elements. Many crucial signaling processes occur at The lipid and protein composition of biological membrane surfaces. The reversible association of membranes varies among organisms, tissues, cells, signaling proteins and their specific recognition of and intracellular organelles. Membrane lipids are target membranes depends on characteristic mem- amphipathic molecules and can self-assemble into brane properties. Therefore, a cell must monitor supramolecular structures such as micelles, bilayers, membrane properties to mount adaptive responses and hexagonal and cubic phases. The most common and maintain organelle identities. Lipids have a pivotal structure, the lamellar lipid bilayer, has various role in membrane remodeling processes and their physicochemical properties including phase behavior, biosynthesis and turnover are tightly regulated. different degrees of fluidity/viscosity, membrane thick- Although the interplay between the chemical com- ness, and bending rigidity that are determined both by position and the physicochemical membrane proper- the molecular composition and membrane curvature ties, especially viscosity, has been appreciated for [1]. Biological membranes are functionalized by the decades, it is still largely unknown how cells sense bulk incorporation of membrane proteins that serve as membrane properties to adjust lipid metabolism. Mass 0022-2836/© 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). J Mol Biol (2016) 428, 4776–4791 Lipid regulation and the homeoviscous response 4777 spectrometry-based lipidomics combined with subcel- otherms, such as mammals, large variations exist lular fractionation or the immunoisolation of organelles between the acyl chain profiles of several tissues, have provided comprehensive insights in lipid diversity suggesting that this profile endows cellular mem- and lipid distribution [2–5]. Eukaryotic cells and their branes with specific properties [14]. Thus, eukaryotic organelles synthesize hundreds to thousands of lipid cells establish lipid gradients, with sterols and molecules differing in their molecular structures, saturated acyl chains being gradually enriched along physicochemical properties, and molar abundances. the secretory pathway at the expense of monounsat- This stunning diversity derives from the combinatorial urated acyl chains (Fig. 2b). Neuronal cells accumu- complexity of the lipid ‘building blocks’ [6] (Fig. 1a). late polyunsaturated acyl chains toward the axon tip, Glycerophospholipids and sphingolipids have a mod- whereas less unsaturated lipids show the opposite ular design featuring two apolar hydrocarbon chains distribution [15]. Similarly, lipid molecules with satu- (or acyl chains) and a hydrophilic headgroup. The acyl rated and polyunsaturated acyl chains are enriched in chains are fatty acids (FAs), fatty alcohols, or the apical plasma membrane of epithelial cells at the long-chain bases differing in length and the number expense of monounsaturated acyl chains [3].Polyun- and positions of double bonds and hydroxylations saturated lipids can adopt different shapes, stabilize (Fig. 1b). The headgroups define the lipid class and are co-existing membrane domains, and facilitate chemically diverse structures spanning from simple membrane deformation normal to the plane of the structures such as choline to complex oligosaccharide membrane [14,16]. Their role in shaping physico- structures. chemical membrane properties for ultra-fast endocy- The proportion of saturated and unsaturated acyl tosis in neurons and signal transduction by chains in membrane lipids is a key factor determining mechano-sensitive channels and photoreceptors lipid packing, membrane viscosity, and water perme- has only recently gained a fresh emphasis [14]. ability [7] (Fig. 2). Poikilothermic organisms including Little is known about how eukaryotic cells sense and bacteria, cyanobacteria, fungi, plants, and fish that do control the acyl chain composition of the membrane not control their body temperature increase the lipids. In this review, we summarize our current proportion of unsaturated acyl chains in membrane mechanistic understanding of membrane sensing by lipids to maintain fluidity in the cold [8–13]. However, the simple eukaryote Saccharomyces cerevisiae and temperature is not the only factor that explains the compare it with prokaryotic strategies in order to unsaturation level of biological membranes. In home- identify common features that might guide our search (a) (b) PC palmitic acid sn-2 16:0 saturated FA sn-1 vaccenic acid PC 16:0/18:1(9Z) 18:1(11Z) monounsaturated FA PE PS PA Ergosterol lactobacillus acid C18:0n-7cyc cyclopropane FA PI PG oleic acid 18:1(9Z) IPC monounsaturated FA arachidonic acid IPC 18:0;3/26:0;1 20:4(5Z,8Z,11Z,14Z) polyunsaturated FA Fig. 1. Membrane lipid and FA complexity. (a) Membrane lipids are subdivided in three major categories: glycerophospholipids (green and gray), sterols (red), and sphingolipids (yellow). Classes of glycerophospholipids are defined by the hydrophilic headgroups (gray) attached to the DAG backbone. The acyl chains in the sn-1 and sn-2 position (green) of the glycerophospholipids contribute to the species diversity within lipid classes. Also sphingolipids constitute a large category of lipids with diverse headgroups and acyl chains. (b) FAs in bacteria and eukaryotes contribute to lipid species diversity. Palmitic, oleic, and arachidonic acid are common in eukaryotic membrane lipids. Vaccenic acid is important for the homeoviscous response in E. coli. Likewise, lactobacillus acid maintains membrane fluidity in E. coli under specific growth conditions. Polyunsaturated FAs found are characterized by a remarkable structural flexibility. Different FAs have, when incorporated in membrane lipids and due to their shape (schematically shown), different impact on physicochemical membrane properties. 4778 Lipid regulation and the homeoviscous response (a) Hydrophobic matrix and membrane fluidity(c) Headgroups and acyl chains determine shape conical cylindrical inverted conical polyunsaturated saturated acyl chains unsaturated acyl chains sterols increase lipid packing non-fluid fluid and membrane thickness (b) Cellular territories (d) Lateral pressure profiles normal bilayer polyunsaturated early secretory pathway late secretory pathway headgroup repulsion acyl chains -- interfacial tension chain repulsion pressure pressure small headgroups membrane curvature - cytosol - -- - interfacial voids high molecular lipid packing almost neutral surface charge negative surface charge inward transport of PS pressure pressure Fig. 2. The lipid composition affects membrane properties including the lateral pressure profile. (a) Lipid acyl chains and sterols