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International Journal of Molecular... May 2019Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the... (Review)
Review
Biological membranes are key elements for the maintenance of cell architecture and physiology. Beyond a pure barrier separating the inner space of the cell from the outer, the plasma membrane is a scaffold and player in cell-to-cell communication and the initiation of intracellular signals among other functions. Critical to this function is the plasma membrane compartmentalization in lipid microdomains that control the localization and productive interactions of proteins involved in cell signal propagation. In addition, cells are divided into compartments limited by other membranes whose integrity and homeostasis are finely controlled, and which determine the identity and function of the different organelles. Here, we review current knowledge on membrane lipid composition in the plasma membrane and endomembrane compartments, emphasizing its role in sustaining organelle structure and function. The correct composition and structure of cell membranes define key pathophysiological aspects of cells. Therefore, we explore the therapeutic potential of manipulating membrane lipid composition with approaches like membrane lipid therapy, aiming to normalize cell functions through the modification of membrane lipid bilayers.
Topics: Animals; Cell Compartmentation; Cell Membrane; Fatty Acids, Unsaturated; Humans; Membrane Lipids; Metabolic Diseases; Neoplasms; Neurodegenerative Diseases
PubMed: 31052427
DOI: 10.3390/ijms20092167 -
Nature Reviews. Molecular Cell Biology Jun 2017Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A... (Review)
Review
Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A large number of studies have focused on understanding the basis for this heterogeneity and its physiological relevance. The membrane raft hypothesis formalized a physicochemical principle for a subtype of such lateral membrane heterogeneity, in which the preferential associations between cholesterol and saturated lipids drive the formation of relatively packed (or ordered) membrane domains that selectively recruit certain lipids and proteins. Recent studies have yielded new insights into this mechanism and its relevance in vivo, owing primarily to the development of improved biochemical and biophysical technologies.
Topics: Animals; Cell Membrane; Humans; Membrane Lipids; Membrane Microdomains
PubMed: 28356571
DOI: 10.1038/nrm.2017.16 -
Biochimica Et Biophysica Acta.... May 2021Transport proteins are essential for cells in allowing the exchange of substances between cells and their environment across the lipid bilayer forming a tight barrier.... (Review)
Review
Transport proteins are essential for cells in allowing the exchange of substances between cells and their environment across the lipid bilayer forming a tight barrier. Membrane lipids modulate the function of transmembrane proteins such as transporters in two ways: Lipids are tightly and specifically bound to transport proteins and in addition they modulate from the bulk of the lipid bilayer the function of transport proteins. This overview summarizes currently available information at the ultrastructural level on lipids tightly bound to transport proteins and the impact of altered bulk membrane lipid composition. Human diseases leading to altered lipid homeostasis will lead to altered membrane lipid composition, which in turn affect the function of transporter proteins.
Topics: Animals; Biological Transport; Humans; Lipid Bilayers; Membrane Lipids; Membrane Transport Proteins; Protein Binding
PubMed: 33476785
DOI: 10.1016/j.bbadis.2021.166079 -
Current Opinion in Lipidology Oct 2017Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 years, however, a... (Review)
Review
PURPOSE OF REVIEW
Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last 3 years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction.
RECENT FINDINGS
In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers. Recent reports have also shown that the degree of saturation of phospholipids can reduce the activation of certain G-protein-coupled receptors, and signaling downstream to Toll-like receptor 4 with consequences to nuclear factor kappa B activation and inflammation. Levels of specific gangliosides in the membrane were reported to activate integrins in a cell-autonomous manner affecting tumor cell migration. Furthermore, high resolution of the association of cholesterol with the smoothened receptor has clarified its participation in sonic hedgehog signaling. These are some of the key advancements that have further propelled our understanding of the broad versatile contributions of membrane lipids in signal transduction.
SUMMARY
As we gain definitive detail regarding the impact of lipid-protein interactions and their consequences to cell function, the options for therapeutic targeting expand with the possibility of greater specificity.
Topics: Animals; Humans; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Phospholipids; Signal Transduction
PubMed: 28692598
DOI: 10.1097/MOL.0000000000000443 -
The New Phytologist Jun 2018Lipid degradation processes are important in microalgae because survival and growth of microalgal cells under fluctuating environmental conditions require permanent... (Review)
Review
Lipid degradation processes are important in microalgae because survival and growth of microalgal cells under fluctuating environmental conditions require permanent remodeling or turnover of membrane lipids as well as rapid mobilization of storage lipids. Lipid catabolism comprises two major spatially and temporarily separated steps, namely lipolysis, which releases fatty acids and head groups and is catalyzed by lipases at membranes or lipid droplets, and degradation of fatty acids to acetyl-CoA, which occurs in peroxisomes through the β-oxidation pathway in green microalgae, and can sometimes occur in mitochondria in some other algal species. Here we review the current knowledge on the enzymes and regulatory proteins involved in lipolysis and peroxisomal β-oxidation and highlight gaps in our understanding of lipid degradation pathways in microalgae. Metabolic use of acetyl-CoA products via glyoxylate cycle and gluconeogenesis is also reviewed. We then present the implication of various cellular processes such as vesicle trafficking, cell cycle and autophagy on lipid turnover. Finally, physiological roles and the manipulation of lipid catabolism for biotechnological applications in microalgae are discussed.
Topics: Acetyl Coenzyme A; Biotechnology; Fatty Acids; Lipid Metabolism; Membrane Lipids; Microalgae
PubMed: 29473650
DOI: 10.1111/nph.15047 -
Biochimica Et Biophysica Acta.... Jan 2021The field of membrane structural biology represents a fast-moving field with exciting developments including native nanodiscs that allow preparation of complexes of...
The field of membrane structural biology represents a fast-moving field with exciting developments including native nanodiscs that allow preparation of complexes of post-translationally modified proteins bound to biological lipids. This has led to conceptual advances including biological membrane:protein assemblies or "memteins" as the fundamental functional units of biological membranes. Tools including cryo-electron microscopy and X-ray crystallography are maturing such that it is becoming increasingly feasible to solve structures of large, multicomponent complexes, while complementary methods including nuclear magnetic resonance spectroscopy yield unique insights into interactions and dynamics. Challenges remain, including elucidating exactly how lipids and ligands are recognized at atomic resolution and transduce signals across asymmetric bilayers. In this special volume some of the latest thinking and methods are gathered through the analysis of a range of transmembrane targets. Ongoing work on areas including polymer design, protein labelling and microfluidic technologies will ensure continued progress on improving resolution and throughput, providing deeper understanding of this most important group of targets.
Topics: Lipid Bilayers; Membrane Lipids; Membrane Proteins; Nanostructures; Nuclear Magnetic Resonance, Biomolecular
PubMed: 32841614
DOI: 10.1016/j.bbamem.2020.183445 -
The Journal of Biological Chemistry Jul 2021Archaeal membrane lipids are structurally different from bacterial and eukaryotic membrane lipids, but little is known about the enzymes involved in their synthesis. In...
Archaeal membrane lipids are structurally different from bacterial and eukaryotic membrane lipids, but little is known about the enzymes involved in their synthesis. In a recent study, Exterkate et al. identified and characterized a cardiolipin synthase from the archaeon Methanospirillum hungatei. This enzyme can synthesize archaeal, bacterial, and mixed archaeal/bacterial cardiolipin species from a wide variety of substrates, some of which are not even naturally occurring. This discovery could revolutionize synthetic lipid biology, being used to construct a variety of lipids with nonnatural head groups and mixed archaeal/bacterial hydrophobic chains.
Topics: Archaea; Bacteria; Membrane Lipids; Membrane Proteins; Methanospirillum; Synthetic Biology; Transferases (Other Substituted Phosphate Groups)
PubMed: 34097872
DOI: 10.1016/j.jbc.2021.100859 -
Chemical Reviews May 2019Membrane lipids interact with proteins in a variety of ways, ranging from providing a stable membrane environment for proteins to being embedded in to detailed roles in... (Review)
Review
Membrane lipids interact with proteins in a variety of ways, ranging from providing a stable membrane environment for proteins to being embedded in to detailed roles in complicated and well-regulated protein functions. Experimental and computational advances are converging in a rapidly expanding research area of lipid-protein interactions. Experimentally, the database of high-resolution membrane protein structures is growing, as are capabilities to identify the complex lipid composition of different membranes, to probe the challenging time and length scales of lipid-protein interactions, and to link lipid-protein interactions to protein function in a variety of proteins. Computationally, more accurate membrane models and more powerful computers now enable a detailed look at lipid-protein interactions and increasing overlap with experimental observations for validation and joint interpretation of simulation and experiment. Here we review papers that use computational approaches to study detailed lipid-protein interactions, together with brief experimental and physiological contexts, aiming at comprehensive coverage of simulation papers in the last five years. Overall, a complex picture of lipid-protein interactions emerges, through a range of mechanisms including modulation of the physical properties of the lipid environment, detailed chemical interactions between lipids and proteins, and key functional roles of very specific lipids binding to well-defined binding sites on proteins. Computationally, despite important limitations, molecular dynamics simulations with current computer power and theoretical models are now in an excellent position to answer detailed questions about lipid-protein interactions.
Topics: Cell Membrane; Computer Simulation; Humans; Ion Channels; Membrane Lipids; Membrane Proteins; Models, Biological; Models, Molecular; Molecular Docking Simulation; Protein Conformation; Receptors, G-Protein-Coupled
PubMed: 30758191
DOI: 10.1021/acs.chemrev.8b00451 -
International Journal of Molecular... Sep 2019Membrane regulators such as sterols and hopanoids play a major role in the physiological and physicochemical adaptation of the different plasmic membranes in Eukarya and... (Review)
Review
Membrane regulators such as sterols and hopanoids play a major role in the physiological and physicochemical adaptation of the different plasmic membranes in Eukarya and Bacteria. They are key to the functionalization and the spatialization of the membrane, and therefore indispensable for the cell cycle. No archaeon has been found to be able to synthesize sterols or hopanoids to date. They also lack homologs of the genes responsible for the synthesis of these membrane regulators. Due to their divergent membrane lipid composition, the question whether archaea require membrane regulators, and if so, what is their nature, remains open. In this review, we review evidence for the existence of membrane regulators in Archaea, and propose tentative location and biological functions. It is likely that no membrane regulator is shared by all archaea, but that they may use different polyterpenes, such as carotenoids, polyprenols, quinones and apolar polyisoprenoids, in response to specific stressors or physiological needs.
Topics: Adaptation, Physiological; Archaea; Cell Membrane; Membrane Lipids
PubMed: 31505830
DOI: 10.3390/ijms20184434 -
Current Opinion in Cell Biology Aug 2023Why has nature acquired such a huge lipid repertoire? Although it would be theoretically possible to make a lipid bilayer fulfilling barrier functions with only one... (Review)
Review
Why has nature acquired such a huge lipid repertoire? Although it would be theoretically possible to make a lipid bilayer fulfilling barrier functions with only one glycerophospholipid, there are diverse and numerous different lipid species. Lipids are heterogeneously distributed across the evolutionary tree with lipidomes evolving in parallel to organismal complexity. Moreover, lipids are different between organs and tissues and even within the same cell, different organelles have characteristic lipid signatures. At the molecular level, membranes are asymmetric and laterally heterogeneous. This lipid asymmetry at different scales indicates that these molecules may play very specific molecular functions in biology. Some of these roles have been recently uncovered: lipids have been shown to be essential in processes such as hypoxia and ferroptosis or in protein sorting and trafficking but many of them remain still unknown. In this review we will discuss the importance of understanding lipid diversity in biology across scales and we will share a toolbox with some of the emerging technologies that are helping us to uncover new lipid molecular functions in cell biology and, step by step, crack the membrane lipid code.
Topics: Membrane Lipids; Lipid Bilayers; Organelles; Cell Membrane
PubMed: 37437490
DOI: 10.1016/j.ceb.2023.102203