Control of membrane fluidity: the OLE pathway in focus

2017 ◽  
Vol 398 (2) ◽  
pp. 215-228 ◽  
Author(s):  
Stephanie Ballweg ◽  
Robert Ernst
Keyword(s):  
Membrane Fluidity ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Membrane Lipids ◽  
Current Knowledge ◽  
Acyl Chain ◽  
Membrane Integrity ◽  
Building Blocks ◽  
Membrane Lipid ◽  
Membrane Properties

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.

scholarly journals Characterization of fatty acid desaturases reveals stress-induced synthesis of C18 unsaturated fatty acids enriched in triacylglycerol in the oleaginous alga Chromochloris zofingiensis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tao Wu ◽  
Lihua Yu ◽  
Yu Zhang ◽  
Jin Liu
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Gas Chromatography Mass Spectrometry ◽  
Transcription Start Sites ◽  
Chromatography Mass Spectrometry ◽  
Chromochloris Zofingiensis

Abstract Background The green microalga Chromochloris zofingiensis is capable of producing high levels of triacylglycerol rich in C18 unsaturated fatty acids (UFAs). FA desaturation degree is regulated by FA desaturases (FADs). Nevertheless, it remains largely unknown regarding what FADs are involved in FA desaturations and how these FADs collaborate to contribute to the high abundance of C18 UFAs in triacylglycerol in C. zofingiensis. Results To address these issues, we firstly determined the transcription start sites of 11 putative membrane-bound FAD-coding genes (CzFADs) and updated their gene models. Functional validation of these CzFADs in yeast and cyanobacterial cells revealed that seven are bona fide FAD enzymes with distinct substrates. Combining the validated functions and predicted subcellular compartments of CzFADs and the FA profiles of C. zofingiensis, the FA desaturation pathways in this alga were reconstructed. Furthermore, a multifaceted lipidomic analysis by systematically integrating thin-layer chromatography, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry techniques was conducted, unraveling profiles of polar membrane lipids in C. zofingiensis and major desaturation steps occurring in these lipids. By correlating transcriptional patterns of CzFAD genes and changes of lipids upon abiotic stress conditions, our results highlighted collaboration of CzFADs for C18 UFA synthesis and supported that both de novo FA synthesis and membrane lipid remodeling contributed C18 UFAs to triacylglycerol for storage. Conclusions Taken together, our study for the first time elucidated the pathways of C18 FA desaturations and comprehensive profiles of polar membrane lipids in C. zofingiensis and shed light on collaboration of CzFADs for the synthesis and enrichment of C18 UFAs in triacylglycerol.

scholarly journals Lipid Acyl Chain Remodeling in Yeast

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S31780 ◽  
Author(s):  
Mike F. Renne ◽  
Xue Bao ◽  
Cedric H. De Smet ◽  
Anton I. P. M. De Kroon
Keyword(s):  
Intracellular Transport ◽  
De Novo ◽  
Acyl Chain ◽  
Model Organism ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Lipid Homeostasis ◽  
Synthetic Process ◽  
Acyl Chains ◽  
Phospholipid Acyl Chain

Membrane lipid homeostasis is maintained by de novo synthesis, intracellular transport, remodeling, and degradation of lipid molecules. Glycerophospholipids, the most abundant structural component of eukaryotic membranes, are subject to acyl chain remodeling, which is defined as the post-synthetic process in which one or both acyl chains are exchanged. Here, we review studies addressing acyl chain remodeling of membrane glycerophospholipids in Saccharomyces cerevisiae, a model organism that has been successfully used to investigate lipid synthesis and its regulation. Experimental evidence for the occurrence of phospholipid acyl chain exchange in cardiolipin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine is summarized, including methods and tools that have been used for detecting remodeling. Progress in the identification of the enzymes involved is reported, and putative functions of acyl chain remodeling in yeast are discussed.

scholarly journals Lipid synthesis in human erythroid cells: the effect of sickling

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 189-195 ◽  
Author(s):  
TA Lane ◽  
SK Ballas ◽  
ER Burka
Keyword(s):  
Cell Membrane ◽  
Neutral Lipid ◽  
Sickle Cell Anemia ◽  
De Novo ◽  
Membrane Lipids ◽  
Membrane Damage ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Erythroid Cell ◽  
Cell Membrane Damage

Abstract Human reticulocytes are capable of synthesizing membrane lipids from 14C-glycerol de novo. In both sickle and nonsickle reticulocytes the majority of 14C-glycerol was incorporated into phospholipids, primarily phosphatidylserine and phosphatidylcholine. Incorporation into sphingomyelin was minimal. The most abundant neutral lipid synthesized was triglyceride. In the absence of sickling, the rate of lipid synthesis in sickle reticulocytes was similar to that of nonsickle reticulocytes. With the induction of sickling under anoxic conditions sickle reticulocytes showed a prompt increase in the rate of lipid synthesis to an average of 69% above control values, while nonsickle reticulocytes under similar conditions decreased the rate of lipid synthesis. An increase in the rate of membrane lipid synthesis is associated in the mammalian erythroid cell with cell membrane damage. The findings further confirm that lesions of the erythroid cell membrane in sickle cell anemia are secondary to the sickling process itself.

scholarly journals Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition

2020 ◽  
Vol 11 ◽  
Author(s):  
Jennifer J. Lühr ◽  
Nils Alex ◽  
Lukas Amon ◽  
Martin Kräter ◽  
Markéta Kubánková ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
T Cell ◽  
T Cell Activation ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Building Blocks ◽  
Membrane Properties ◽  
Antigen Uptake ◽  
Peripheral Tissues

Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest lymph node, and find their way into the correct position in the net of the lymph node microenvironment to meet and interact with the respective T cells. We hypothesize that the maturation of DCs is well prepared and optimized leading to processes that alter various cellular characteristics from mechanics and metabolism to membrane properties. Here, we investigated the mechanical properties of monocyte-derived dendritic cells (moDCs) using real-time deformability cytometry to measure cytoskeletal changes and found that mature moDCs were stiffer compared to immature moDCs. These cellular changes likely play an important role in the processes of cell migration and T cell activation. As lipids constitute the building blocks of the plasma membrane, which, during maturation, need to adapt to the environment for migration and DC-T cell interaction, we performed an unbiased high-throughput lipidomics screening to identify the lipidome of moDCs. These analyses revealed that the overall lipid composition was significantly changed during moDC maturation, even implying an increase of storage lipids and differences of the relative abundance of membrane lipids upon maturation. Further, metadata analyses demonstrated that lipid changes were associated with the serum low-density lipoprotein (LDL) and cholesterol levels in the blood of the donors. Finally, using lipid packing imaging we found that the membrane of mature moDCs revealed a higher fluidity compared to immature moDCs. This comprehensive and quantitative characterization of maturation associated changes in moDCs sets the stage for improving their use in clinical application.

Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties

Microbiology ◽  
2005 ◽  
Vol 151 (8) ◽  
pp. 2529-2542 ◽  
Author(s):  
Christine Baysse ◽  
Méabh Cullinane ◽  
Valérie Dénervaud ◽  
Elizabeth Burrowes ◽  
J. Maxwell Dow ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Membrane Fluidity ◽  
Environmental Conditions ◽  
Adaptive Response ◽  
Environmental Changes ◽  
Membrane Lipids ◽  
Phospholipid Composition ◽  
Genetically Engineered ◽  
Membrane Properties

Changes in the cellular envelope are major physiological adaptations that occur when micro-organisms encounter extreme environmental conditions. An appropriate degree of membrane fluidity is crucial for survival, and alteration of membrane lipids is an essential adaptive response. Emerging data suggest that microbial cells may recognize alterations in their membrane viscosity resulting from certain environmental changes as a trigger for adaptive cellular responses. In Pseudomonas aeruginosa, the quorum-sensing (QS) system involves a complex regulatory circuitry that coordinates the expression of genes according to a critical population density. Interestingly, it has been shown that the QS system of P. aeruginosa can also be activated by nutritional stress, independently of the cell density, and therefore may be part of a more general adaptive response to stressful environmental conditions. In order to examine the proposed link between membrane properties and stress signalling, the effects of genetically engineered alterations of the membrane phospholipid composition of P. aeruginosa PAO1 on the activation of the stringent response and the QS system were examined. The lptA gene encoding a functional homologue of PlsC, an Escherichia coli enzyme that catalyses the second step of the phospholipid biosynthesis pathway, was identified and disrupted. Inactivation of lptA altered the fatty acid profile of phospholipids and the membrane properties, resulting in decreased membrane fluidity. This resulted in a premature production of the QS signals N-butanoyl- and N-hexanoyl-homoserine lactone (C4-HSL and C6-HSL) and a repression of 2-heptyl-3-hydroxy-4-quinolone (PQS) synthesis at later growth phases. The effects on C4- and C6-HSL depended upon the expression of relA, encoding the (p)ppGpp alarmone synthase, which was increased in the lptA mutant. Together, the findings support the concept that alterations in membrane properties can act as a trigger for stress-related gene expression.

Defense peptides: recent developments

2015 ◽  
Vol 6 (4) ◽  
pp. 237-251 ◽  
Author(s):  
Małgorzata Cytryńska ◽  
Agnieszka Zdybicka-Barabas
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Membrane Lipid ◽  
Factors Affecting ◽  
Natural Defense ◽  
Secreted Factors ◽  
Recent Developments ◽  
Extracellular Proteinases ◽  
Defense Peptides ◽  
Conventional Antibiotics

AbstractDefense peptides are small amphipathic molecules that exhibit antimicrobial, antitumor, antiviral, and immunomodulatory properties. This review summarizes current knowledge on the mechanisms of antimicrobial activity of cationic and anionic defense peptides, indicating peptide-based as well as microbial cell-based factors affecting this activity. The peptide-based factors include charge, hydrophibicity, and amphipathicity, whereas the pathogen-based factors are membrane lipid composition, presence of sterols, membrane fluidity, cell wall components, and secreted factors such as extracellular proteinases. Since defense peptides have been considered very promising molecules that could replace conventional antibiotics in the era of drug-resistant pathogens, the issue of microbial resistance to antimicrobial peptides (AMPs) is addressed. Furthermore, selected approaches employed for optimization and de novo design of effective AMPs based on the properties recognized as important for the function of natural defense peptides are presented.

Effects of malnutrition on microvillus membrane glucose transport and physical properties

1990 ◽  
Vol 259 (6) ◽  
pp. G940-G946 ◽  
Author(s):  
J. D. Butzner ◽  
P. D. Brockway ◽  
J. B. Meddings
Keyword(s):  
Membrane Protein ◽  
Physical Properties ◽  
Membrane Fluidity ◽  
Glucose Transport ◽  
Membrane Lipids ◽  
Protein Energy Malnutrition ◽  
Membrane Lipid ◽  
Protein Energy ◽  
Sodium Dependent ◽  
Microvillus Membrane

We examined sodium-dependent glucose transport, membrane lipid composition, and membrane fluidity in microvillus membrane vesicles isolated from the distal intestine of infant rabbits subjected to protein-energy malnutrition and age-matched controls. In vesicles from malnourished animals, sodium-dependent glucose transport was significantly enhanced, as evidenced by a twofold increase in maximal transport capacity, Jmax. Carrier affinity for glucose, as assessed by the Km of the transport process, was unaffected. These alternations were associated with marked changes in microvillus membrane composition. Malnourished animals had an increase in the lipid-to-protein ratio of the microvillus membrane, which suggests that malnutrition might be associated with either a reduction in membrane protein or an increase in membrane lipid. This would be expected to increase the fluidity of the microvillus membrane. However, we observed no differences in either the static or dynamic component of membrane fluidity, using multiple fluorescent probes, between dietary groups. Further analysis of membrane lipids was undertaken to establish whether quantitative differences in lipid subclasses could explain this discrepancy. We found that nutrient deprivation produced numerous alterations in membrane lipids. The major findings were an increase in both the cholesterol-to-phospholipid and phosphatidylethanolamine-to-phosphatidylcholine ratios. Both alterations would be expected to decrease membrane fluidity and presumably represent a compensatory response to the loss of membrane protein. Thus chronic postnatal protein-energy malnutrition initiates several adaptive responses that include major alterations in the chemical composition of the microvillus membrane. The resulting effect preserves efficient glucose transport and maintains the physical properties of the microvillus membrane.

scholarly journals Revealing Further Insights on Chilling Injury of Postharvest Bananas by Untargeted Lipidomics

Foods ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 894 ◽  
Author(s):  
Juan Liu ◽  
Qingxin Li ◽  
Junjia Chen ◽  
Yueming Jiang
Keyword(s):  
Fatty Acids ◽  
Low Temperature ◽  
Unsaturated Fatty Acids ◽  
Membrane Lipids ◽  
Saturated Fatty Acids ◽  
Chilling Injury ◽  
Membrane Damage ◽  
Membrane Lipid ◽  
Banana Fruit ◽  
Control Fruit

Chilling injury is especially prominent in postharvest bananas stored at low temperature below 13 °C. To elucidate better the relationship between cell membrane lipids and chilling injury, an untargeted lipidomics approach using ultra-performance liquid chromatography–mass spectrometry was conducted. Banana fruit were stored at 6 °C for 0 (control) and 4 days and then sampled for lipid analysis. After 4 days of storage, banana peel exhibited a marked chilling injury symptom. Furthermore, 45 lipid compounds, including glycerophospholipids, saccharolipids, and glycerolipids, were identified with significant changes in peel tissues of bananas stored for 4 days compared with the control fruit. In addition, higher ratio of digalactosyldiacylglycerol (DGDG) to monogalactosyldiacylglycerol (MGDG) and higher levels of phosphatidic acid (PA) and saturated fatty acids but lower levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and unsaturated fatty acids were observed in banana fruit with chilling injury in contrast to the control fruit. Meanwhile, higher activities of phospholipase D (PLD) and lipoxygenase (LOX) were associated with significantly upregulated gene expressions of MaPLD1 and MaLOX2 and higher malondialdehyde (MDA) content in chilling injury-related bananas. In conclusion, our study indicated that membrane lipid degradation resulted from reduced PC and PE, but accumulated PA, while membrane lipid peroxidation resulted from the elevated saturation of fatty acids, resulting in membrane damage which subsequently accelerated the chilling injury occurrence of banana fruit during storage at low temperature.

scholarly journals Effect of high levels of CO2 and O2 on membrane fatty acid profile and membrane physiology of meat spoilage bacteria

2021 ◽  
Author(s):  
Sandra Kolbeck ◽  
Hermine Kienberger ◽  
Karin Kleigrewe ◽  
Maik Hilgarth ◽  
Rudi F. Vogel
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Membrane Fluidity ◽  
Fatty Acid Profile ◽  
Membrane Lipid ◽  
Membrane Properties ◽  
Meat Spoilage ◽  
Spoilage Bacteria ◽  
The Impact ◽  
Membrane Physiology

AbstractThe membrane is the major protective barrier separating the cell from the environment and is thus important for bacteria to survive environmental stress. This study investigates changes in membrane lipid compositions and membrane physiology of meat spoiling bacteria in response to high CO2 (30%) and O2 (70%) concentrations, as commonly used for modified atmosphere packaging of meat. Therefore, the fatty acid profile as well as membrane fluidity, permeability and cell surface were determined and correlated to the genomic settings of five meat spoiling bacteria Brochothrix (B.) thermosphacta, Carnobacterium (C.) divergens, C. maltaromaticum, Leuconostoc (L.) gelidum subsp. gelidum and L. gelidum subsp. gasicomitatum cultivated under different gas atmospheres. We identified different genomic potentials for fatty acid adaptations, which were in accordance with actual measured changes in the fatty acid composition for each species in response to CO2 and/or O2, e.g., an increase in saturated, iso and cyclopropane fatty acids. Even though fatty acid changes were species-specific, the general physiological responses were similar, comprising a decreased membrane permeability and fluidity. Thus, we concluded that meat spoiling bacteria facilitate a change in membrane fatty acids upon exposure to O2 and CO2, what leads to alteration of membrane fluidity and permeability. The observed adaptations might contribute to the resistance of meat spoilers against detrimental effects of the gases O2 and CO2 and thus help to explain their ability to grow under different modified atmospheres. Furthermore, this study provides fundamental knowledge regarding the impact of fatty acid changes on important membrane properties of bacteria.

scholarly journals Branched chain fatty acid synthesis drives tissue-specific innate immune response and  infection dynamics of  Staphylococcus aureus

2021 ◽  
Vol 17 (9) ◽  
pp. e1009930
Author(s):  
Xi Chen ◽  
Wei Ping Teoh ◽  
Madison R. Stock ◽  
Zachary J. Resko ◽  
Francis Alonzo
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Membrane Fluidity ◽  
Unsaturated Fatty Acids ◽  
Cell Envelope ◽  
Acyl Chain ◽  
Dependent Manner ◽  
Infection Dynamics ◽  
Branched Chain

Fatty acid-derived acyl chains of phospholipids and lipoproteins are central to bacterial membrane fluidity and lipoprotein function. Though it can incorporate exogenous unsaturated fatty acids (UFA), Staphylococcus aureus synthesizes branched chain fatty acids (BCFA), not UFA, to modulate or increase membrane fluidity. However, both endogenous BCFA and exogenous UFA can be attached to bacterial lipoproteins. Furthermore, S. aureus membrane lipid content varies based upon the amount of exogenous lipid in the environment. Thus far, the relevance of acyl chain diversity within the S. aureus cell envelope is limited to the observation that attachment of UFA to lipoproteins enhances cytokine secretion by cell lines in a TLR2-dependent manner. Here, we leveraged a BCFA auxotroph of S. aureus and determined that driving UFA incorporation disrupted infection dynamics and increased cytokine production in the liver during systemic infection of mice. In contrast, infection of TLR2-deficient mice restored inflammatory cytokines and bacterial burden to wildtype levels, linking the shift in acyl chain composition toward UFA to detrimental immune activation in vivo. In in vitro studies, bacterial lipoproteins isolated from UFA-supplemented cultures were resistant to lipase-mediated ester hydrolysis and exhibited heightened TLR2-dependent innate cell activation, whereas lipoproteins with BCFA esters were completely inactivated after lipase treatment. These results suggest that de novo synthesis of BCFA reduces lipoprotein-mediated TLR2 activation and improves lipase-mediated hydrolysis making it an important determinant of innate immunity. Overall, this study highlights the potential relevance of cell envelope acyl chain repertoire in infection dynamics of bacterial pathogens.

Sign in / Sign up

Export Citation Format

Share Document