Progress in lipid research最新文献

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute one of the largest families of lipid-binding/transfer proteins (LTPs) in eukaryotes. The current view is that many of them mediate inter-organelle lipid transfer over membrane contact sites (MCS). The transfer occurs in several cases in a ‘counter-current’ fashion: A lipid such as cholesterol or phosphatidylserine (PS) is transferred against its concentration gradient driven by transport of a phosphoinositide in the opposite direction. In this way ORPs are envisioned to maintain the distinct organelle lipid compositions, with impacts on multiple organelle functions. However, the functions of ORPs extend beyond lipid homeostasis to regulation of processes such as cell survival, proliferation and migration. Important expanding areas of mammalian ORP research include their roles in viral and bacterial infections, cancers, and neuronal function.

The yeast OSBP homologue (Osh) proteins execute multifaceted functions in sterol and glycerophospholipid homeostasis, post-Golgi vesicle transport, phosphatidylinositol-4-phosphate, sphingolipid and target of rapamycin (TOR) signalling, and cell cycle control. These observations identify ORPs as lipid transporters and coordinators of signals with an unforeseen variety of cellular processes. Understanding their activities not only enlightens the biology of the living cell but also allows their employment as targets of new therapeutic approaches for disease.

Cell membranes are the initial site of stimulus perception from environment and phospholipids are the basic and important components of cell membranes. Phospholipases hydrolyze membrane lipids to generate various cellular mediators. These phospholipase-derived products, such as diacylglycerol, phosphatidic acid, inositol phosphates, lysophopsholipids, and free fatty acids, act as second messengers, playing vital roles in signal transduction during plant growth, development, and stress responses. This review focuses on the structure, substrate specificities, reaction requirements, and acting mechanism of several phospholipase families. It will discuss their functional significance in plant growth, development, and stress responses. In addition, it will highlight some critical knowledge gaps in the action mechanism, metabolic and signaling roles of these phospholipases and their products in the context of plant growth, development and stress responses.

Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.

Cognitive processes, particularly learning and memory, are crucial brain mechanisms mediating the successful adaptation of individuals to constantly changing environmental conditions. Impairments in memory performance during neurodegenerative disorders or dementias affect life quality of patients as well as their relatives and careers, and thus have a severe socio-economic impact. The last decades have viewed learning and memory as predominantly protein-mediated process at the synapses of brain neurons. However, recent developments propose a principally new, lipid-based mechanism that regulates cognition. Thereby, crucial members of cell membranes, the sphingolipids, emerged to play an outstanding role in learning and memory. The most abundant brain sphingolipids, ceramides and gangliosides, dynamically shape the composition of protein carrying cellular membranes. This, in turn, regulates protein signaling through the membranes and overall neuronal plasticity. An imbalance in sphingolipid composition and disrupted dynamics significantly affect normal functioning of cells and results in the development of multiple psychiatric and neurological disorders with cognitive impairments. Ceramides and gangliosides interact with a plethora of molecular pathways determining de novo learning and memory, as well as pathogenic pathways of neurodegenerative disorders and dementias of various origins. Considering sphingolipids as a trigger mechanism for learning and memory under physiological and pathological conditions, a principally new class of lipid-based preventive and therapeutic approaches to target cognitive impairments and dementias is emerging.

The lipid composition of cellular membranes can impact a number of physiological processes such as signaling, cell migration, endocytosis and intracellular transport. In this article we focus on some aspects concerning analysis of lipids and research on lipid structure and function in mammalian cells that in our opinion have not obtained sufficient attention. This includes interleaflet coupling between the two layers of the membrane, and the role of lipid species, i.e. the role of the complete structure of the lipids, including lipid chain length and the position of double bonds. We highlight the role of PS species for membrane function. We also discuss the large diversity of PS species in different biological samples and the possible functional consequences, and we provide an overview of PS species from 40 different samples. Furthermore, recent studies show that there seems to be a coregulation concerning the levels of sphingolipids and ether lipids. We review and discuss the published data indicating such a coregulation. Moreover, we point to some of the pitfalls in the field of lipidomics and present suggestions for improvement. Finally, we discuss the importance of using asymmetric membrane models with a composition of lipid species that are common in biological membranes.

The mammary gland undergoes a spectacular series of changes during its development and maintains a remarkable capacity to remodel and regenerate during progression through the lactation cycle. This flexibility of the mammary gland requires coordination of multiple processes including cell proliferation, differentiation, regeneration, stress response, immune activity, and metabolic changes under the control of diverse cellular and hormonal signaling pathways. The lactating mammary epithelium orchestrates synthesis and apical secretion of macromolecules including milk lipids, milk proteins, and lactose as well as other minor nutrients that constitute milk. Knowledge about the subcellular compartmentalization of these metabolic and signaling events, as they relate to milk production and secretion during lactation, is expanding. Here we review how major organelles (endoplasmic reticulum, Golgi apparatus, mitochondrion, lysosome, and exosome) within mammary epithelial cells collaborate to initiate, mediate, and maintain lactation, and how study of these organelles provides insight into options to maintain mammary/breast health.

Matrix-assisted laser desorption and ionization (MALDI) mass spectrometry (MS) is an indispensable tool in modern lipid research since it is fast, sensitive, tolerates sample impurities and provides spectra without major analyte fragmentation.

We will discuss some methodological aspects, the related ion-forming processes and the MALDI MS characteristics of the different lipid classes (with the focus on glycerophospholipids) and the progress, which was achieved during the last ten years. Particular attention will be given to quantitative aspects of MALDI MS since this is widely considered as the most serious drawback of the method. Although the detailed role of the matrix is not yet completely understood, it will be explicitly shown that the careful choice of the matrix is crucial (besides the careful evaluation of the positive and negative ion mass spectra) in order to be able to detect all lipid classes of interest.

Two developments will be highlighted: spatially resolved Imaging MS is nowadays well established and the distribution of lipids in tissues merits increasing interest because lipids are readily detectable and represent ubiquitous compounds. It will also be shown that a combination of MALDI MS with thin-layer chromatography (TLC) enables a fast spatially resolved screening of an entire TLC plate which makes the method competitive with LC/MS.

The ‘standard’ fluid-mosaic membrane model can provide a framework for the operation of the photosynthetic and respiratory electron transport systems, the generation of the proton motive force (pmf) and its utilization for ATP synthesis according to the chemiosmotic theory. However, this model, with the bilayer organization of all lipid molecules, assigns no function to non-bilayer lipids – while in recent years it became clear that the two fundamental energy transducing membranes of the biosphere, chloroplast thylakoid membranes (TMs) and inner mitochondrial membranes (IMMs), contain large amounts of non-bilayer (non-lamellar) lipid phases.

In this review, we summarize our understanding on the role of non-lamellar phases in TMs and IMMs: (i) We propose that for these membrane vesicles the dynamic exchange model (DEM) provides a more suitable framework than the ‘standard’ model; DEM complements the ‘standard’ model by assuming the co-existence of bilayer and non-bilayer phases and their interactions, which contribute to the structural dynamics of the membrane systems and safe-guard the membranes’ high protein:lipid ratios. (ii) Non-bilayer phases play pivotal roles in membrane fusion and intermembrane lipid exchanges – essential processes in the self-assembly of these highly folded intricate membranes. (iii) The photoprotective, lipocalin-like lumenal enzyme, violaxanthin de-epoxidase, in its active state requires the presence of non-bilayer lipid phase. (iv) Cardiotoxins, water-soluble polypeptides, induce non-bilayer phases in mitochondria. (v) ATP synthesis, in mammalian heart IMMs, is positively correlated with the amount of non-bilayer packed lipids with restricted mobility. (vi) The hypothesized sub-compartments, due to non-lamellar phases, are proposed to enhance the utilization of pmf and might contribute to the recently documented functional independence of individual cristae within the same mitochondrion. Further research is needed to identify and characterize the structural entities associated with the observed non-bilayer phases; and albeit fundamental questions remain to be elucidated, non-lamellar lipid phases should be considered on a par with the bilayer phase, with which they co-exist in functional TMs and IMMs.

Lipids participate in diverse biological functions including signal transduction, cellular membrane biogenesis and carbon storage. Following de novo biosynthesis in the plastids, fatty acids (FAs) are transported as acyl-CoA esters to the endoplasmic reticulum where glycerol-3-phosphate undergoes a series of acyl-CoA-dependent acylation via the Kennedy pathway to form triacylglycerols for subsequent assembly into oils. Alternatively, newly synthesized FAs are incorporated into phosphatidylcholine (PC) by a PC:acyl-CoA exchange process defined as “acyl editing”. Acyl-CoA-binding proteins (ACBPs) at various subcellular locations can function in lipid transfer by binding and transporting acyl-CoA esters and maintaining intracellular acyl-CoA pools. Widely distributed in the plant kingdom, ACBPs are found in all eukaryotes and some eubacteria. In both rice and Arabidopsis, six forms of ACBPs co-exist and are classified into four groups based on their functional domains. Their conserved four-helix structure facilitates interaction with acyl-CoA esters. ACBPs also interact with phospholipids as well as protein partners and function in seed oil regulation, development, pathogen defense and stress responses. Besides the ACBPs, other proteins such as the lipid transfer proteins (LTPs), annexins and lipid droplet-associated proteins are also important lipid-binding proteins. While annexins bind Ca²⁺ and phospholipids, LTPs transport lipid molecules including FAs, acyl-CoA esters and phospholipids.

Marine ecosystems are rich in “omega-3” long-chain (C_20-24) polyunsaturated fatty acids (LC-PUFA). Their production has been historically accepted to derive mostly from marine microbes. This long-standing dogma has been challenged recently by the discovery that numerous invertebrates, mostly with an aquatic life-style, have the enzyme machinery necessary for the de novo biosynthesis of polyunsaturated fatty acids (PUFA) and, from them, LC-PUFA. The key breakthrough was the detection in these animals of enzymes called “methyl-end desaturases” enabling PUFA de novo biosynthesis. Moreover, other enzymes with pivotal roles in LC-PUFA biosynthesis, including front-end desaturases and elongation of very long- chain fatty acids proteins, have been characterised in several non-vertebrate animal phyla. This review provides a comprehensive overview of the complement and functions of these gene/protein families in aquatic animals, particularly invertebrates and fish. Therefore, we expand and re-define our previous revision of the LC-PUFA biosynthetic enzymes present in chordates to animals as a whole, discussing how key genomic events have determined the diversity and distribution of desaturase and elongase genes in different taxa. We conclude that both invertebrates and fish display active, but markedly different, LC-PUFA biosynthetic gene networks that result from a complex evolutionary path combined with functional diversification and plasticity.