scholarly journals Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 919
Author(s):  
Manuel Torres ◽  
Sebastià Parets ◽  
Javier Fernández-Díaz ◽  
Roberto Beteta-Göbel ◽  
Raquel Rodríguez-Lorca ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Therapeutic Potential ◽  
Membrane Lipid ◽  
Fatty Acyl ◽  
Bioactive Lipids ◽  
Membrane Lipid Composition ◽  
Membrane Structure And Function ◽  
And Function

Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).

scholarly journals ThePI3‐kinasePI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition

FEBS Letters ◽  
2018 ◽  
Vol 593 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Maria V. Selvadurai ◽  
Rose J. Brazilek ◽  
Mitchell J. Moon ◽  
Jean‐Yves Rinckel ◽  
Anita Eckly ◽  
...  
Keyword(s):  
Lipid Composition ◽  
Membrane Structure ◽  
Membrane Lipid ◽  
Structure And Function ◽  
Platelet Membrane ◽  
Membrane Lipid Composition ◽  
Membrane Structure And Function ◽  
And Function

scholarly journals Membrane Lipid Composition: Effect on Membrane and Organelle Structure, Function and Compartmentalization and Therapeutic Avenues

2019 ◽  
Vol 20 (9) ◽  
pp. 2167 ◽  
Author(s):  
Doralicia Casares ◽  
Pablo V. Escribá ◽  
Catalina Ana Rosselló
Keyword(s):  
Plasma Membrane ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signal Propagation ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Cell Functions ◽  
And Function

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.

scholarly journals Effect of membrane environment on the activity and inhibitability by malonyl-CoA of the carnitine acyltransferase of hepatic microsomal membranes

1997 ◽  
Vol 322 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Neil M. BROADWAY ◽  
E. David SAGGERSON
Keyword(s):  
Lipid Composition ◽  
Membrane Lipids ◽  
Specific Activity ◽  
Membrane Lipid ◽  
Microsomal Membrane ◽  
Membrane Lipid Composition ◽  
Carnitine Acyltransferase ◽  
Malonyl Coa ◽  
Microsomal Membranes ◽  
Myristoyl Coa

We have investigated the extent to which membrane environment affects the catalytic properties of the malonyl-CoA-sensitive carnitine acyltransferase of liver microsomal membranes. Arrhenius-type plots of activity were linear in the absence and presence of malonyl-CoA (2.5 μM). Sensitivity to malonyl-CoA increased with decreasing assay temperature. Partly purified enzyme displayed an increased K0.5 (substrate concentration supporting half the maximal reaction rate) for myristoyl-CoA and a reduced sensitivity to malonyl-CoA compared with the enzyme in situ in membranes. Reconstitution with liposomes of a range of compositions restored the K0.5 for myristoyl-CoA to values similar to that seen in native membranes. The lipid requirements for restoration of sensitivity to malonyl-CoA were more stringent. When animals were starved for 24 h the specific activity of carnitine acyltransferase in microsomal membrane residues was increased 3.3-fold, whereas sensitivity to malonyl-CoA was decreased to 1/2.8. When enzymes partly purified from fed and starved animals were reconstituted into crude soybean phosphatidylcholine liposomes there was no difference in sensitivity to malonyl-CoA. When partly purified enzyme from fed rats was reconstituted into liposomes prepared from microsomal membrane lipids from fed animals it was 2.2-fold more sensitive to malonyl-CoA than when reconstituted with liposomes prepared from microsomal membrane lipids from starved animals. This suggests that the physiological changes in sensitivity to malonyl-CoA are mediated via changes in membrane lipid composition rather than via modification of the enzyme protein itself. The increased specific actvity of acyltransferase observed on starvation could not be attributed to changes in membrane lipid composition.

Influence of membrane lipid composition on the structure and activity of γ-secretase

2018 ◽  
Vol 20 (43) ◽  
pp. 27294-27304 ◽  
Author(s):  
Rodrigo Aguayo-Ortiz ◽  
John E. Straub ◽  
Laura Dominguez
Keyword(s):  
Computational Modeling ◽  
Lipid Composition ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Bilayer Lipid ◽  
Modeling Approaches ◽  
And Function ◽  
Structural Ensemble ◽  
Structure And Activity ◽  
Insight Into

Insight into the effect of bilayer lipid composition on the GS structural ensemble and function using multiscale computational modeling approaches.

scholarly journals Intact Membrane Lipids of “Candidatus Nitrosopumilus maritimus,” a Cultivated Representative of the Cosmopolitan Mesophilic Group I Crenarchaeota

2008 ◽  
Vol 74 (8) ◽  
pp. 2433-2440 ◽  
Author(s):  
Stefan Schouten ◽  
Ellen C. Hopmans ◽  
Marianne Baas ◽  
Henry Boumann ◽  
Sonja Standfest ◽  
...  
Keyword(s):  
Polar Lipid ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Lipid Analysis ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
The Core ◽  
Group I ◽  
Head Groups ◽  
Intact Membrane

ABSTRACT In this study we analyzed the membrane lipid composition of “Candidatus Nitrosopumilus maritimus,” the only cultivated representative of the cosmopolitan group I crenarchaeota and the only mesophilic isolate of the phylum Crenarchaeota. The core lipids of “Ca. Nitrosopumilus maritimus” consisted of glycerol dialkyl glycerol tetraethers (GDGTs) with zero to four cyclopentyl moieties. Crenarchaeol, a unique GDGT containing a cyclohexyl moiety in addition to four cyclopentyl moieties, was the most abundant GDGT. This confirms unambiguously that crenarchaeol is synthesized by species belonging to the group I.1a crenarchaeota. Intact polar lipid analysis revealed that the GDGTs have hexose, dihexose, and/or phosphohexose head groups. Similar polar lipids were previously found in deeply buried sediments from the Peru margin, suggesting that they were in part synthesized by group I crenarchaeota.

scholarly journals Membrane Synthesis, Specific Lipid Requirements, and Localized Lipid Composition Changes Associated with a Positive-Strand RNA Virus RNA Replication Protein

2003 ◽  
Vol 77 (23) ◽  
pp. 12819-12828 ◽  
Author(s):  
Wai-Ming Lee ◽  
Paul Ahlquist
Keyword(s):  
Lipid Composition ◽  
Rna Synthesis ◽  
Membrane Lipids ◽  
Rna Virus ◽  
Rna Replication ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna ◽  
Total Membrane

ABSTRACT Multifunctional RNA replication protein 1a of brome mosaic virus (BMV), a positive-strand RNA virus, localizes to the cytoplasmic face of endoplasmic reticulum (ER) membranes and induces ER lumenal spherules in which viral RNA synthesis occurs. We previously showed that BMV RNA replication in yeast is severely inhibited prior to negative-strand RNA synthesis by a single-amino-acid substitution in the ole1w allele of yeast Δ9 fatty acid (FA) desaturase, which converts saturated FAs (SFAs) to unsaturated FAs (UFAs). Here we further define the relationships between 1a, membrane lipid composition, and RNA synthesis. We show that 1a expression increases total membrane lipids in wild-type (wt) yeast by 25 to 33%, consistent with recent results indicating that the numerous 1a-induced spherules are enveloped by invaginations of the outer ER membrane. 1a did not alter total membrane lipid composition in wt or ole1w yeast, but the ole1w mutation selectively depleted 18-carbon, monounsaturated (18:1) FA chains and increased 16:0 SFA chains, reducing the UFA-to-SFA ratio from ∼2.5 to ∼1.5. Thus, ole1w inhibition of RNA replication was correlated with decreased levels of UFA, membrane fluidity, and plasticity. The ole1w mutation did not alter 1a-induced membrane synthesis, 1a localization to the perinuclear ER, or colocalization of BMV 2a polymerase, nor did it block spherule formation. Moreover, BMV RNA replication templates were still recovered from cell lysates in a 1a-induced, 1a- and membrane-associated, and nuclease-resistant but detergent-susceptible state consistent with spherules. However, unlike nearby ER membranes, the membranes surrounding spherules in ole1w cells were not distinctively stained with osmium tetroxide, which interacts specifically with UFA double bonds. Thus, in ole1w cells, spherule-associated membranes were locally depleted in UFAs. This localized UFA depletion helps to explain why BMV RNA replication is more sensitive than cell growth to reduced UFA levels. The results imply that 1a preferentially interacts with one or more types of membrane lipids.

scholarly journals FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung-Min Lee ◽  
Seol Hee Lee ◽  
Youngae Jung ◽  
Younglang Lee ◽  
Jong Hyun Yoon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Er Stress ◽  
Lipid Composition ◽  
Membrane Lipid ◽  
Muscle Recovery ◽  
Membrane Lipid Composition ◽  
And Function ◽  
Muscle Homeostasis

Abstract Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. Here we report that FABP3 is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that FABP3 overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. FABP3-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. FABP3 knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, FABP3 reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, FABP3 drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.

scholarly journals Heat Adaptation Alters Escherichia coli O157:H7 Membrane Lipid Composition and Verotoxin Production

2003 ◽  
Vol 69 (9) ◽  
pp. 5115-5119 ◽  
Author(s):  
Hyun-Gyun Yuk ◽  
Douglas L. Marshall
Keyword(s):  
Escherichia Coli ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Vaccenic Acid ◽  
Membrane Lipid ◽  
Membrane Lipid Composition ◽  
E Coli ◽  
Heat Adaptation ◽  
Mutant Strains ◽  
Composition Changes

ABSTRACT The influence of heat adaptation (growth at 42 and 45°C) on changes in membrane lipid composition and verotoxin concentration of Escherichia coli O157:H7 (ATCC 43895), an rpoS mutant of ATCC 43895 (FRIK 816-3), a verotoxin mutant E. coli O157:H7 (B6-914), and nonpathogenic E. coli (ATCC 25922) was investigated. D values (57°C) of heat-adapted cells were up to 3.9 min longer than those of control cells for all four strains. Heat adaptation increased the amounts of palmitic acid (16:0) and cis-vaccenic acid (18:1ω7c) in membrane lipids of ATCC 43895 and the rpoS mutant, whereas there was a reduction and no change in the amount of cis-vaccenic acid in nonpathogenic and verotoxin mutant E. coli, respectively. The ratio of palmitic to cis-vaccenic acids decreased in ATCC 43895 and in the rpoS mutant, whereas the ratio increased in nonpathogenic E. coli and was not different in the verotoxin mutant with elevated growth temperature. Total verotoxin concentration decreased due to a reduction in intracellular verotoxin amount in heat-adapted ATCC 43895 and rpoS mutant strains. However, extracellular verotoxin concentration increased in heat-adapted cells. The rpoS gene did not influence membrane lipid composition changes although it did affect heat resistance. Results suggest that increased membrane fluidity may have caused increased verotoxin secretion.

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