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Journal of Lipid Research May 2005Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid... (Review)
Review
Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, "lipidomics," in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases.
Topics: Database Management Systems; Lipids; Molecular Structure; Terminology as Topic
PubMed: 15722563
DOI: 10.1194/jlr.E400004-JLR200 -
The Journal of Biological Chemistry May 1957
Topics: Lipids
PubMed: 13428781
DOI: No ID Found -
International Journal of Molecular... Sep 2020Apolipoprotein E () is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of... (Review)
Review
Apolipoprotein E () is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance and degradation of amyloid β (Aβ) and neuroinflammation. In humans, the gene has three common allelic variants, termed E2, E3, and E4. is considered the strongest genetic risk factor for Alzheimer's disease (AD), whereas is neuroprotective. To perform its normal functions, apoE must be secreted and properly lipidated, a process influenced by the structural differences associated with apoE isoforms. Here we highlight the importance of lipidated apoE as well as the -lipidation targeted therapeutic approaches that have the potential to correct or prevent neurodegeneration. Many of these approaches have been validated using diverse cellular and animal models. Overall, there is great potential to improve the lipidated state of apoE with the goal of ameliorating -associated central nervous system impairments.
Topics: Alzheimer Disease; Animals; Apolipoproteins E; Humans; Lipids; Neuroprotective Agents
PubMed: 32882843
DOI: 10.3390/ijms21176336 -
FEBS Letters Apr 2018Various yeasts, both conventional and exotic ones, are known to produce compounds useful to mankind. Ethanol is the most known of these compounds, but more complex... (Review)
Review
Various yeasts, both conventional and exotic ones, are known to produce compounds useful to mankind. Ethanol is the most known of these compounds, but more complex molecules such as amphiphilic biosurfactants can also be derived from eukaryotic microorganisms at an industrially and commercially relevant scale. Among them, glycolipids are the most promising, due to their attractive properties and high product titers. Many of these compounds can be considered as secondary metabolites with a specific function for the host. Hence, a dedicated biosynthetic process enables regulation and combines pathways delivering the lipidic moiety and the hydrophilic carbohydrate part of the glycolipid. In this Review, we will discuss the biosynthetic and regulatory aspects of the yeast-derived sophorolipids, mannosylerythritol lipids, and cellobiose lipids, with special emphasis on the relation between glycolipid synthesis and the general lipid metabolism.
Topics: Glycolipids; Oleic Acids; Saccharomyces cerevisiae; Surface-Active Agents
PubMed: 29067677
DOI: 10.1002/1873-3468.12888 -
The Journal of Membrane Biology Dec 2022Membrane fusion plays a lead role in the transport of vesicles, neurotransmission, mitochondrial dynamics, and viral infection. There are fusion proteins that catalyze... (Review)
Review
Membrane fusion plays a lead role in the transport of vesicles, neurotransmission, mitochondrial dynamics, and viral infection. There are fusion proteins that catalyze and regulate the fusion. Interestingly, various types of fusion proteins are present in nature and they possess diverse mechanisms of action. We have highlighted the importance of the functional domains of intracellular heterotypic fusion, homotypic endoplasmic reticulum (ER), homotypic mitochondrial, and type-I viral fusion. During intracellular heterotypic fusion, the SNAREs and four-helix bundle formation are prevalent. Type-I viral fusion is controlled by the membrane destabilizing properties of fusion peptide and six-helix bundle formation. The ER/mitochondrial homotypic fusion is controlled by GTPase activity and the membrane destabilization properties of the amphipathic helix(s). Although the mechanism of action of these fusion proteins is diverse, they have some similarities. In all cases, the lipid composition of the membrane greatly affects membrane fusion. Next, examples of lipidation of the fusion proteins were discussed. We suggest that the fatty acyl hydrophobic tail not only acts as an anchor but may also modulate the energetics of membrane fusion intermediates. Lipidation is also important to design more effective peptide-based fusion inhibitors. Together, we have shown that membrane lipid composition and lipidation are important to modulate membrane fusion.
Topics: Membrane Fusion; GTP Phosphohydrolases; Endoplasmic Reticulum; Mitochondrial Dynamics; Lipids
PubMed: 36102950
DOI: 10.1007/s00232-022-00267-5 -
Bioconjugate Chemistry Aug 2021The development of lipopeptides (lipidated peptides) for vaccines is discussed, including their role as antigens and/or adjuvants. Distinct classes of lipopeptide... (Review)
Review
The development of lipopeptides (lipidated peptides) for vaccines is discussed, including their role as antigens and/or adjuvants. Distinct classes of lipopeptide architectures are covered including simple linear and ligated constructs and lipid core peptides. The design, synthesis, and immunological responses of the important class of glycerol-based Toll-like receptor agonist lipopeptides such as PamCSK, which contains three palmitoyl chains and a CSK hexapeptide sequence, and many derivatives of this model immunogenic compound are also reviewed. Self-assembled lipopeptide structures including spherical and worm-like micelles that have been shown to act as vaccine agents are also described. The work discussed includes examples of lipopeptides developed with model antigens, as well as for immunotherapies to treat many infectious diseases including malaria, influenza, hepatitis, COVID-19, and many others, as well as cancer immunotherapies. Some of these have proceeded to clinical development. The research discussed highlights the huge potential of, and diversity of roles for, lipopeptides in contemporary and future vaccine development.
Topics: Animals; Humans; Lipopeptides; Vaccines
PubMed: 34228433
DOI: 10.1021/acs.bioconjchem.1c00258 -
Cell Structure and Function May 2023Protein-lipid conjugation is a widespread modification involved in many biological processes. Various lipids, including fatty acids, isoprenoids, sterols,... (Review)
Review
Protein-lipid conjugation is a widespread modification involved in many biological processes. Various lipids, including fatty acids, isoprenoids, sterols, glycosylphosphatidylinositol, sphingolipids, and phospholipids, are covalently linked with proteins. These modifications direct proteins to intracellular membranes through the hydrophobic nature of lipids. Some of these membrane-binding processes are reversible through delipidation or by reducing the affinity to membranes. Many signaling molecules undergo lipid modification, and their membrane binding is important for proper signal transduction. The conjugation of proteins to lipids also influences the dynamics and function of organellar membranes. Dysregulation of lipidation has been associated with diseases such as neurodegenerative diseases. In this review, we first provide an overview of diverse forms of protein-lipid conjugation and then summarize the catalytic mechanisms, regulation, and roles of these modifications.Key words: lipid, lipidation, membrane, organelle, protein modification.
Topics: Proteins; Fatty Acids; Phospholipids; Lipid Metabolism; Sterols; Cell Membrane
PubMed: 37019684
DOI: 10.1247/csf.23016 -
Developmental Cell Jul 2023Lipid droplets (LDs) store lipids that can be utilized during times of scarcity via autophagic and lysosomal pathways, but how LDs and autophagosomes interact remained...
Lipid droplets (LDs) store lipids that can be utilized during times of scarcity via autophagic and lysosomal pathways, but how LDs and autophagosomes interact remained unclear. Here, we discovered that the E2 autophagic enzyme, ATG3, localizes to the surface of certain ultra-large LDs in differentiated murine 3T3-L1 adipocytes or Huh7 human liver cells undergoing prolonged starvation. Subsequently, ATG3 lipidates microtubule-associated protein 1 light-chain 3B (LC3B) to these LDs. In vitro, ATG3 could bind alone to purified and artificial LDs to mediate this lipidation reaction. We observed that LC3B-lipidated LDs were consistently in close proximity to collections of LC3B-membranes and were lacking Plin1. This phenotype is distinct from macrolipophagy, but it required autophagy because it disappeared following ATG5 or Beclin1 knockout. Our data suggest that extended starvation triggers a noncanonical autophagy mechanism, similar to LC3B-associated phagocytosis, in which the surface of large LDs serves as an LC3B lipidation platform for autophagic processes.
Topics: Animals; Humans; Mice; Autophagosomes; Autophagy; Autophagy-Related Protein 5; Lipid Droplets; Microtubule-Associated Proteins
PubMed: 37315562
DOI: 10.1016/j.devcel.2023.05.009 -
The EMBO Journal Sep 2005The cellular lipidome comprises over 1000 different lipids. Most lipids look similar having a polar head and hydrophobic tails. Still, cells recognize lipids with... (Review)
Review
The cellular lipidome comprises over 1000 different lipids. Most lipids look similar having a polar head and hydrophobic tails. Still, cells recognize lipids with exquisite specificity. The functionality of lipids is determined by their local concentration, which varies between organelles, between the two leaflets of the lipid bilayer and even within the lateral plane of the membrane. To incorporate function, cellular lipidomics must not only determine which lipids are present but also the concentration of each lipid at each specific intracellular location in time and the lipid's interaction partners. Moreover, cellular lipidomics must include the enzymes of lipid metabolism and transport, their specificity, localization and regulation. Finally, it requires a thorough understanding of the physical properties of lipids and membranes, especially lipid-lipid and lipid-protein interactions. In the context of a cell, the complex relationships between metabolites can only be understood by viewing them as an integrated system. Cellular lipidomics provides a framework for understanding and manipulating the vital role of lipids, especially in membrane transport and sorting and in cell signaling.
Topics: Animals; Biological Transport; Cells; Humans; Lipid Metabolism; Lipids; Membrane Microdomains; Organelles
PubMed: 16138081
DOI: 10.1038/sj.emboj.7600798 -
Genetics Dec 2018Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an... (Review)
Review
Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.
Topics: Adipose Tissue; Animals; Biological Evolution; Biological Transport; Drosophila melanogaster; Lipid Metabolism; Lipids; Signal Transduction; Triglycerides
PubMed: 30523167
DOI: 10.1534/genetics.118.301583