Showing papers on "Membrane lipids published in 2017"
TL;DR: By correlating interfacial strength with the presence of interfacial lipids, the development of a mass spectrometry platform provides a rationale for understanding the role of lipids in both transient and stable interactions within a range of α-helical membrane proteins, including G-protein-coupled receptors.
Abstract: Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways but is often difficult to define or predict. Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and to uncover how lipids act as key regulators of membrane-protein association. Evaluation of oligomeric strength for a dataset of 125 α-helical oligomeric membrane proteins reveals an absence of interfacial lipids in the mass spectra of 12 membrane proteins with high oligomeric stability. For the bacterial homologue of the eukaryotic biogenic transporters (LeuT, one of the proteins with the lowest oligomeric stability), we found a precise cohort of lipids within the dimer interface. Delipidation, mutation of lipid-binding sites or expression in cardiolipin-deficient Escherichia coli abrogated dimer formation. Molecular dynamics simulation revealed that cardiolipin acts as a bidentate ligand, bridging across subunits. Subsequently, we show that for the Vibrio splendidus sugar transporter SemiSWEET, another protein with low oligomeric stability, cardiolipin shifts the equilibrium from monomer to functional dimer. We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E. coli, which has the lowest oligomeric strength, but not for the substantially more stable homologous Thermus thermophilus protein NapA. We found that lipid binding is obligatory for dimerization of NhaA, whereas NapA has adapted to form an interface that is stable without lipids. Overall, by correlating interfacial strength with the presence of interfacial lipids, we provide a rationale for understanding the role of lipids in both transient and stable interactions within a range of α-helical membrane proteins, including G-protein-coupled receptors.
319 citations
TL;DR: It is shown that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction and are demonstrated to be generalized to other signaling pathways.
Abstract: Membranes made of molecules called lipids surround every living cell to protect the cell's contents. Cells also communicate with the outside environment via their membranes. Proteins in the membrane receive information from the environment and trigger signaling pathways inside the cell to relay this information to the center of cell. The way in which proteins are organized on the membrane has a major influence on their signaling activity. Some areas of the membrane are more crowded with certain lipids and signaling proteins than others. Lipid and protein molecules of particular types can come together and form distinct areas called “ordered” and “disordered” domains. The lipids in ordered domains are more tightly packed than disordered domains and it is thought that this difference allows domains to selectively exclude or include certain proteins. Ordered domains are also known as "lipid rafts". Lipid rafts and disordered domains may help cells to control the activities of signaling pathways, however, technical limitations have made it difficult to study the roles of these domains. The membranes surrounding immune cells called B cells contain a protein called the B cell receptor, which engages with proteins from microbes and other foreign invaders. When the B cell receptor binds to a foreign protein it forms clusters with other B cell receptors and becomes active, triggering a signaling pathway that leads to immune responses. Stone, Shelby et al. examined lipid rafts and disordered domains in B cells from mice using a technique called super-resolution fluorescence microscopy. The results show that clusters of B cell receptors are present within lipid rafts. These clusters made the lipid rafts larger and more stable. A protein that is needed during the early stages of B cell receptor signaling was also found in the same lipid rafts. Another protein that terminates signaling was excluded because it prefers disordered domains. Together, this provides a local environment in certain areas of the membrane that favors receptor activity and supports the subsequent immune response. Future work is needed to understand how cells control the make-up of lipids and proteins within their membranes, and how defects in this regulation can alter signaling activity and lead to disease.
188 citations
TL;DR: A realistically complex human brain plasma membrane (PM) lipid model is developed and test and previous work on an idealized, “average” mammalian PM is extended, showing both striking similarities, despite significantly different lipid composition, and interesting differences.
181 citations
TL;DR: Some key regulatory mechanisms that control ER‐localized enzyme activities in animal cells are highlighted and how they act in concert to maintain cellular lipid homeostasis is discussed, as well as how their dysregulation contributes to human disease.
Abstract: Endoplasmic reticulum (ER)‐localized enzymes synthesize the vast majority of cellular lipids. The ER therefore has a major influence on cellular lipid biomass and balances the production of different lipid categories, classes, and species. Signals from outside and inside the cell are directed to ER‐localized enzymes, and lipid enzyme activities are defined by the integration of internal, homeostatic, and external information. This allows ER‐localized lipid synthesis to provide the cell with membrane lipids for growth, proliferation, and differentiation‐based changes in morphology and structure, and to maintain membrane homeostasis across the cell. ER enzymes also respond to physiological signals to drive carbohydrates and nutritionally derived lipids into energy‐storing triglycerides. In this review, we highlight some key regulatory mechanisms that control ER‐localized enzyme activities in animal cells. We also discuss how they act in concert to maintain cellular lipid homeostasis, as well as how their dysregulation contributes to human disease.
151 citations
TL;DR: As definitive detail is gained 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.
Abstract: Purpose of reviewReception 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 o
144 citations
TL;DR: The structure determination of mouse TMEM16A by cryo-electron microscopy and a complementary functional characterization reveals the structural basis of anion conduction in a TM EM16 channel and it defines the foundation for the diverse functional behavior in the TMEM15 family.
Abstract: Cell membranes are made up of two layers of oily molecules, called lipids, embedded with a variety of proteins. Each type of membrane protein carries out a particular activity for the cell, and many are involved in transporting other molecules from one side of the membrane to the other. The TMEM16 proteins are a large family of membrane proteins. Most are known as lipid scramblases and move lipids between the two layers of the membrane. However, some TMEM16 proteins transport ions in or out of the cell, and are instead called ion channels. TMEM16 proteins are found in animals, plants and fungi but not bacteria, and play key roles in many biological activities that keep these organisms alive. For example, in humans, ion channels belonging to the TMEM16 family help keep the lining of the lung moist, and allow muscles in the gut to contract. The structure of a scramblase shows that two protein units interact, with each unit containing a furrow that spans the membrane, through which lipids can move from one layer to the other. However, to date, the shape of a TMEM16 ion channel has not been determined. It was therefore not clear how a protein with features that let it transport large, oily molecules like lipids had evolved to transport small, charged particles instead. TMEM16A is a member of the TMEM16 family that transports negatively charged chloride ions. Using a technique called cryo-electron microscopy, Paulino et al. have determined the three-dimensional shape of the version of TMEM16A from a mouse. Overall, TMEM16A is organized similarly to the lipid scramblase. However, some parts of the TMEM16A protein have undergone rearrangements such that the membrane-exposed furrow that provides a path for lipids in scramblases is now partially sealed in TMEM16A. This results in an enclosed pore that is largely shielded from the oily membrane and through which ions can pass. Additionally, biochemical analysis suggests that TMEM16A forms a narrow pore that may widen towards the side facing the inside of the cell, though further work is needed to understand if this is relevant to the protein’s activity. The three-dimensional structure of TMEM16A reveals how the protein’s architecture differs from other family members working as lipid scramblases. It also gives insight into how TMEM16 proteins might work as ion channels. These findings can now form a strong basis for future studies into the activity of TMEM16 proteins.
131 citations
TL;DR: Overall, it is shown that cholesterol's impact on A2AR-binding affinity goes beyond pure allosteric modulation and unveils a new interaction mode between cholesterol and the A2 AR that could potentially apply to other GPCRs.
Abstract: Cholesterol is a key component of cell membranes with a proven modulatory role on the function and ligand-binding properties of G-protein-coupled receptors (GPCRs). Crystal structures of prototypical GPCRs such as the adenosine A2A receptor (A2AR) have confirmed that cholesterol finds stable binding sites at the receptor surface suggesting an allosteric role of this lipid. Here we combine experimental and computational approaches to show that cholesterol can spontaneously enter the A2AR-binding pocket from the membrane milieu using the same portal gate previously suggested for opsin ligands. We confirm the presence of cholesterol inside the receptor by chemical modification of the A2AR interior in a biotinylation assay. Overall, we show that cholesterol's impact on A2AR-binding affinity goes beyond pure allosteric modulation and unveils a new interaction mode between cholesterol and the A2AR that could potentially apply to other GPCRs.
129 citations
TL;DR: Overall, the findings reveal a crucial role for TAG metabolism in membrane lipid breakdown, fatty acid turnover, and plant survival under extended darkness.
Abstract: Neutral lipid metabolism is a key aspect of intracellular homeostasis and energy balance and plays a vital role in cell survival under adverse conditions, including nutrient deprivation in yeast and mammals, but the role of triacylglycerol (TAG) metabolism in plant stress response remains largely unknown By thoroughly characterizing mutants defective in SUGAR-DEPENDENT1 (SDP1) triacylglycerol lipase or PEROXISOMAL ABC TRANSPORTER 1 (PXA1), here we show that TAG is a key intermediate in the mobilization of fatty acids from membrane lipids for peroxisomal β-oxidation under prolonged dark treatment Disruption of SDP1 increased TAG accumulation in cytosolic lipid droplets and markedly enhanced plant tolerance to extended darkness We demonstrate that blocking TAG hydrolysis enhances plant tolerance to dark treatment via two distinct mechanisms In pxa1 mutants, in which free fatty acids accumulated rapidly under extended darkness, SDP1 disruption resulted in a marked decrease in levels of cytotoxic lipid intermediates such as free fatty acids and phosphatidic acid, suggesting a buffer function of TAG accumulation against lipotoxicity under fatty acid overload In the wild type, in which free fatty acids remained low and unchanged under dark treatment, disruption of SDP1 caused a decrease in reactive oxygen species production and hence the level of lipid peroxidation, indicating a role of TAG in protection against oxidative damage Overall, our findings reveal a crucial role for TAG metabolism in membrane lipid breakdown, fatty acid turnover, and plant survival under extended darkness
104 citations
TL;DR: This review considers hydrophobic matching of the intramembranous proteolipid boundary to explain the conformational changes and oligomeric states of proteins within the bilayer.
Abstract: Membrane lipids and cellular water (soft matter) are becoming increasingly recognized as key determinants of protein structure and function Their influences can be ascribed to modulation of the bilayer properties or to specific binding and allosteric regulation of protein activity In this review, we first consider hydrophobic matching of the intramembranous proteolipid boundary to explain the conformational changes and oligomeric states of proteins within the bilayer Alternatively, membranes can be viewed as complex fluids, whose properties are linked to key biological functions Critical behavior and nonideal mixing of the lipids have been proposed to explain how raft-like microstructures involving cholesterol affect membrane protein activity Furthermore, the persistence length for lipid–protein interactions suggests the curvature force field of the membrane comes into play A flexible surface model describes how curvature and hydrophobic forces lead to the emergence of new protein functional states
98 citations
TL;DR: Members of the Ups/PRELI family are identified as specific lipid transfer proteins in mitochondria that shuttle phospholipids between mitochondrial membranes, unravelling an intimate crosstalk of membrane lipid transport and homeostasis with the structural organization of mitochondria.
93 citations
TL;DR: The evidence that membrane charges and membrane-associated calcium regulate phosphorylation of the TCR–CD3 complex is reviewed, and it is proposed that charged lipids, ions in solution, and transient protein interactions form a dynamic equilibrium during T cell activation.
Abstract: While membrane models now include the heterogeneous distribution of lipids, the impact of membrane charges on regulating the association of proteins with the plasma membrane is often overlooked. Charged lipids are asymmetrically distributed between the two leaflets of the plasma membrane, resulting in the inner leaflet being negatively charged and a surface potential that attracts and binds positively charged ions, proteins and peptide motifs. These interactions not only create a transmembrane potential, they can also facilitate the formation of charged membrane domains. Here we reference fields outside of immunology in which consequences of membrane charge are better characterised to highlight important mechanisms. We then focus on T cell receptor (TCR) signalling, reviewing the evidence that membrane charges and membrane-associate calcium regulate phosphorylation of the TCR-CD3 complex and discuss how the immunological synapse exhibits distinct patterns of membrane charge distribution. We propose that charged lipids, ions in solution and transient protein interactions form a dynamic equilibrium during T cell activation.
TL;DR: These simulations provide a comprehensive molecular characterization of the unique surface properties of LDs and suggest how the molecular properties of the surface lipid monolayer can be modulated by the underlying neutral lipids.
TL;DR: This study demonstrates that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries, and shows that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries.
Abstract: It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.
TL;DR: Current knowledge of the OLE pathway is summarized, the best-characterized, eukaryotic sense-and-control system regulating membrane lipid saturation is identified, and open questions to indicate future directions are identified.
Abstract: The maintenance of a fluid lipid bilayer is key for membrane integrity and cell viability We are only beginning to understand how eukaryotic cells sense and maintain the characteristic lipid compositions and bulk membrane properties of their organelles One of the key factors determining membrane fluidity and phase behavior is the proportion of saturated and unsaturated acyl chains in membrane lipids Saccharomyces cerevisiae is an ideal model organism to study the regulation of the lipid acyl chain composition via the OLE pathway The OLE pathway comprises all steps involved in the regulated mobilization of the transcription factors Mga2 and Spt23 from the endoplasmic reticulum (ER), which then drive the expression of OLE1 in the nucleus OLE1 encodes for the essential Δ9-fatty acid desaturase Ole1 and is crucial for de novo biosynthesis of unsaturated fatty acids (UFAs) that are used as lipid building blocks This review summarizes our current knowledge of the OLE pathway, the best-characterized, eukaryotic sense-and-control system regulating membrane lipid saturation, and identifies open questions to indicate future directions
TL;DR: Bacterial lipids are widespread in Bacteria but absent in Archaea and Eukarya, and present knowledge on bacterial lipids was obtained from only a few bacterial species, so the full scale of lipid diversity in bacteria is probably only starting to unravel.
TL;DR: Evidence is highlighted suggesting that PE is a strong candidate to be explored as a potential molecular target for membrane targeted novel anticancer therapy, and may be a strategy that may be effective against tumors that respond poorly to current chemotherapeutic agents.
Abstract: Cancer mortality and morbidity is projected to increase significantly over the next few decades. Current chemotherapeutic strategies have significant limitations, and there is great interest in seeking novel therapies which are capable of specifically targeting cancer cells. Given that fundamental differences exist between the cellular membranes of healthy cells and tumour cells, novel therapies based on targeting membrane lipids in cancer cells is a promising approach that deserves attention in the field of anticancer drug development. Phosphatidylethanolamine (PE), a lipid membrane component which exists only in the inner leaflet of cell membrane under normal circumstances, has increased surface representation on the outer membrane of tumor cells with disrupted membrane asymmetry. . PE thus represents a potential chemotherapeutic target as the higher exposure of PE on the membrane surface of cancer cells. This feature as well as a high degree of expression of PE on endothelial cells in tumour vasculature, makes PE an attractive molecular target for future cancer interventions. There have already been several small molecules and membrane-active peptides identified which bind specifically to the PE molecules on the cancer cell membrane, subsequently inducing membrane disruption leading to cell lysis. This approach opens up a new front in the battle against cancer, and is of particular interest as it may be a strategy that may be prove effective against tumours that respond poorly to current chemotherapeutic agents. We aim to highlight the evidence suggesting that PE is a strong candidate to be explored as a potential molecular target for membrane
TL;DR: Two uncultured archaeal groups are found to reflect the 'archaea-to-eukaryote' membrane transition stage which have led to the current 'lipid divide', and their genetic capacity to synthesize G3P-based 'chimeric lipids' is revealed.
Abstract: Summary
The lipid membrane is one of the most characteristic traits distinguishing the three domains of life. Membrane lipids of Bacteria and Eukarya are composed of fatty acids linked to glycerol-3-phosphate (G3P) via ester bonds, while those of Archaea possess isoprene-based alkyl chains linked by ether linkages to glycerol-1-phosphate (G1P), resulting in the opposite stereochemistry of the glycerol phosphate backbone. This ‘lipid divide’ has raised questions on the evolution of microbial life since eukaryotes are thought to have evolved from the Archaea, requiring a radical change in membrane composition. Here, we searched for homologs of enzymes involved in membrane lipid and fatty acid synthesis in a wide variety of archaeal genomes and performed phylogenomic analyses. We found that two uncultured archaeal groups, i.e. marine euryarchaeota group II/III and ‘Lokiarchaeota’, recently discovered descendants of the archaeal ancestor leading to eukaryotes, lack the gene to synthesize G1P and, consequently, the capacity to synthesize archaeal membrane lipids. However, our analyses reveal their genetic capacity to synthesize G3P-based ‘chimeric lipids’ with either two ether-bound isoprenoidal chains or with an ester-bound fatty acid instead of an ether-bound isoprenoid. These archaea may reflect the ‘archaea-to-eukaryote’ membrane transition stage which have led to the current ‘lipid divide’.
TL;DR: Owing to their fast lipid-exchange kinetics, SMALPs represent highly dynamic equilibrium rather than kinetically trapped membrane mimics, which has important implications for studying protein/lipid interactions in polymer-bounded nanodiscs.
Abstract: Some styrene/maleic acid (SMA) copolymers solubilise membrane lipids and proteins to form polymer-bounded nanodiscs termed SMA/lipid particles (SMALPs). Although SMALPs preserve a lipid-bilayer core, they appear to be more dynamic than other membrane mimics. We used time-resolved Forster resonance energy transfer and small-angle neutron scattering to determine the kinetics and the mechanisms of phospholipid transfer among SMALPs. In contrast with vesicles or protein-bounded nanodiscs, SMALPs exchange lipids not only by monomer diffusion but also by fast collisional transfer. Under typical experimental conditions, lipid exchange occurs within seconds in the case of SMALPs but takes minutes to days in the other bilayer particles. The diffusional and second-order collisional exchange rate constants for SMALPs at 30 °C are kdif = 0.287 s(-1) and kcol = 222 M(-1)s(-1), respectively. Together with the fast kinetics, the observed invariability of the rate constants with probe hydrophobicity and the moderate activation enthalpy of ~70 kJ mol(-1) imply that lipids exchange through a "hydrocarbon continuum" enabled by the flexible nature of the SMA belt surrounding the lipid-bilayer core. Owing to their fast lipid-exchange kinetics, SMALPs represent highly dynamic equilibrium rather than kinetically trapped membrane mimics, which has important implications for studying protein/lipid interactions in polymer-bounded nanodiscs.
TL;DR: It is demonstrated that the restriction of HIV-1 particle infectivity by SERINC5 does not depend on alterations in lipid composition and organization of HIV -1 particles and suggest that channeling serine into lipid biosynthesis may not be a cardinal cellular function ofSERINC5.
TL;DR: Based on the knowledge on the specific cyclodextrin-lipid interactions, cyclodeXTrin derivatives are able to selectively remove certain lipid components from model and biological membranes and can be selected making possible to modulate the lipid profile in such membranes.
Abstract: Lipids being hydrophobic or amphiphilic can be encapsulated by cyclodextrin complexation. Among the various groups of lipids cholesterol, fatty acids, phospholipids and sphingolipids are overviewed concerning the structural requirements for both the lipid and the cyclodextrin component of the complexes. The chain length and the number and position of the double bonds in the fatty acids, the polarity of the head-group in the phospholipids and sphingolipids are important factors. Concerning the cyclodextrins, in addition to the most crucial cavity size also the chemical microenvironment of cavity entrances determine the interaction with lipids. While fatty acids, phospholipids and sphingolipids prefer the alpha-cyclodextrin cavity, cholesterol is complexed first of all by the beta-cyclodextrin and its derivatives. Methylated beta-cyclodextrin has extreme affinity to all of these lipids, which are common constituents of cell membranes. Based on the knowledge on the specific cyclodextrin-lipid interactions, cyclodextrin derivatives are able to selectively remove certain lipid components from model and biological membranes and can be selected making possible to modulate the lipid profile in such membranes.
TL;DR: This Account summarizes the research efforts directed toward developing a deep physical and chemical understanding of protein-free lipid flip-flop in phospholipid membrane models using sum-frequency vibrational spectroscopy (SFVS).
Abstract: ConspectusOur current view of cellular membranes centers on the fluid-mosaic model, which envisions the cellular membrane as a “liquidlike” bilayer of lipids, cholesterol, and proteins that freely diffuse in two dimensions. In stark contrast, the exchange of materials between the leaflets of a bilayer was presumed to be prohibited by the large enthalpic barrier associated with translocating hydrophilic materials, such as a charged lipid headgroup, through the hydrophobic membrane core. This static picture with regard to lipid translocation (or “flip-flop” as it is affectionately known) has been a long-held belief in the study of membrane dynamics. The current accepted membrane model invokes specific protein flippase (inward moving), floppase (outward moving), and scramblase (bidirectional) enzymes that assist in the movement of lipids between the leaflets of cellular membranes. The low rate of protein-free lipid flip-flop has also been a cornerstone of our understanding of the bilateral organization of ce...
TL;DR: It is found that SMA displays no significant lipid preference in homogeneous binary lipid mixtures in the fluid phase, even when using lipids that by themselves show very different solubilization kinetics, and in heterogeneous phase-separated bilayers, SMA was found to have a strong preference for solubILization of lipids inThe fluid phase as compared to those in either a gel phase or a liquid-ordered phase.
Abstract: A promising tool in membrane research is the use of the styrene-maleic acid (SMA) copolymer to solubilize membranes in the form of nanodiscs. Since membranes are heterogeneous in composition, it is important to know whether SMA thereby has a preference for solubilization of either specific types of lipids or specific bilayer phases. Here, we investigated this by performing partial solubilization of model membranes and analyzing the lipid composition of the solubilized fraction. We found that SMA displays no significant lipid preference in homogeneous binary lipid mixtures in the fluid phase, even when using lipids that by themselves show very different solubilization kinetics. By contrast, in heterogeneous phase-separated bilayers, SMA was found to have a strong preference for solubilization of lipids in the fluid phase as compared to those in either a gel phase or a liquid-ordered phase. Together the results suggest that (1) SMA is a reliable tool to characterize native interactions between membrane constituents, (2) any solubilization preference of SMA is not due to properties of individual lipids but rather due to properties of the membrane or membrane domains in which these lipids reside and (3) exploiting SMA resistance rather than detergent resistance may be an attractive approach for the isolation of ordered domains from biological membranes.
TL;DR: Measurements on cell-derived membrane vesicles, in the plasma membrane of live cells, and on single virus particles, show the high potential of polarity-sensitive membrane dyes for probing nanoscale membrane heterogeneity.
TL;DR: Recent work on the structure and function of membrane proteins that have been encapsulated like this in a polymer-bound lipid bilayer are outlined, and the potential for the future with this approach is outlined.
TL;DR: It is speculated that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate large-scale conformational changes within the membrane.
Abstract: Na+/H+ antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the conformational stability and lipid-binding properties of the Na+/H+ exchanger NapA from Thermus thermophilus and compare this to the prototypical antiporter NhaA from Escherichia coli and the human homologue NHA2. We find that NapA and NHA2, but not NhaA, form stable dimers and do not selectively retain membrane lipids. By comparing wild-type NapA with engineered variants, we show that the unfolding of the protein in the gas phase involves the disruption of inter-domain contacts. Lipids around the domain interface protect the native fold in the gas phase by mediating contacts between the mobile protein segments. We speculate that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate large-scale conformational changes within the membrane.
TL;DR: Experimental and molecular dynamics simulations converge to reveal that 5-HT contributes to the termination of lipid peroxidation by direct interaction with active groups of these lipids and could also contribute to limit the production of new radicals.
TL;DR: Analysis of lipid levels in mutants with defects in the two 9-LOX genes revealed that the strong increase in free 9-hydroxy- and 9-keto-fatty acids is dependent on LOX1 but not LOX5, indicating that 9- LOX products contribute to but are not the major cause of loss of germination during aging.
Abstract: Storage of seeds is accompanied by loss of germination and oxidation of storage and membrane lipids. A lipidomic analysis revealed that during natural and artificial aging of Arabidopsis seeds, levels of several diacylglycerols and free fatty acids, such as linoleic acid and linolenic acid as well as free oxidized fatty acids and oxygenated triacylglycerols, increased. Lipids can be oxidized by enzymatic or non-enzymatic processes. In the enzymatic pathway, lipoxygenases (LOXs) catalyze the first oxygenation step of polyunsaturated fatty acids. Analysis of lipid levels in mutants with defects in the two 9-LOX genes revealed that the strong increase in free 9-hydroxy- and 9-keto-fatty acids is dependent on LOX1 but not LOX5. Fatty acid oxidation correlated with an aging-induced decrease of germination, raising the question of whether these oxylipins negatively regulate germination. However, seeds of the lox1 mutant were only slightly more tolerant to aging, indicating that 9-LOX products contribute to but are not the major cause of loss of germination during aging. In contrast to free oxidized fatty acids, accumulation of oxygenated triacylglycerols upon accelerated aging was mainly based on non-enzymatic oxidation of seed storage lipids.
TL;DR: My group was able to establish, contrary to common assumption, that phospholipid environment is a strong determining factor in the function of membrane proteins, and showed that molecular genetic alterations in membrane lipid composition result in many phenotypes.
TL;DR: A review of the genotoxic properties of selected lipid oxidation products important in the context of pathophysiological developments together with a chapter on epigenetic modifications.
TL;DR: This study will help to understand the regulation of glycerolipids metabolism at both biochemical and molecular biological levels in 18:3 plants and to decipher the roles played by lipid remodeling in cold response in major field crop maize.
Abstract: Membrane lipid modulation is one of the major strategies plants have developed for cold acclimation. In this study, a combined lipidomic and transcriptomic analysis was conducted, and the changes in glycerolipids contents and species, and transcriptional regulation of lipid metabolism in maize leaves under low temperature treatment (5°C) were investigated. The lipidomic analysis showed an increase in the phospholipid phosphatidic acid (PA) and a decrease in phosphatidylcholine (PC). And an increase in digalactosyldiacylglycerol and a decrease in monogalactosyldiacylglycerol of the galactolipid class. The results implied an enhanced turnover of PC to PA to serve as precursors for galactolipid synthesis under following low temperature treatment. The analysis of changes in abundance of various lipid molecular species suggested major alterations of different pathways of plastidic lipids synthesis in maize under cold treatment. The synchronous transcriptomic analysis revealed that genes involved in phospholipid and galactolipid synthesis pathways were significantly up-regulated, and a comprehensive gene-metabolite network was generated illustrating activated membrane lipids adjustment in maize leaves following cold treatment. This study will help to understand the regulation of glycerolipids metabolism at both biochemical and molecular biological levels in 18:3 plants and to decipher the roles played by lipid remodeling in cold response in major field crop maize.