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Membrane Sterols

Xiaokui Gu, Wei Xue, Yajing Yin, Hongwei Liu, Shaojie Li, Xianyun Sun
Heat Shock Protein 90 (Hsp90) is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of Neurospora crassa mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes) to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast), Aha1, and P23 (Sba1 in yeast) were required for the basal resistance to antifungal azoles and heat stress...
2016: Frontiers in Microbiology
Nuria Roldan, Thomas K M Nyholm, J Peter Slotte, Jesús Pérez-Gil, Begoña García-Álvarez
To allow breathing and prevent alveolar collapse, lung surfactant (LS) develops a complex membranous system at the respiratory surface. LS is defined by a specific protein and lipid composition, including saturated and unsaturated phospholipid species and cholesterol. Surfactant protein C (SP-C) has been suggested to be an essential element for sustaining the presence of cholesterol in surfactant without functional impairment. In this work, we used a fluorescent sterol-partitioning assay to assess the effect of the surfactant proteins SP-B and SP-C on cholesterol distribution in membranes...
October 18, 2016: Biophysical Journal
Derell Hardman, Daniel McFalls, Stylianos Fakas
Phosphatidic acid phosphatase (PAP) catalyzes the committed step of triacylglycerol (TAG) biosynthesis and thus regulates the amounts of TAG produced by the cell. TAG is the target of biotechnological processes developed for the production of food lipids or biofuels. These processes are using oleaginous microorganisms like the yeast Yarrowia lipolytica as the TAG producers. Thus manipulating key enzymatic activities like PAP in Y. lipolytica could drive lipid biosynthesis towards TAG production and increase TAG yields...
October 15, 2016: Yeast
R Preston Mason, Robert F Jacob, Sandeep Shrivastava, Samuel C R Sherratt, Amitabha Chattopadhyay
Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65...
October 5, 2016: Biochimica et Biophysica Acta
Martin Weichert, Alexander Lichius, Bert-Ewald Priegnitz, Ulrike Brandt, Johannes Gottschalk, Thorben Nawrath, Ulrike Groenhagen, Nick D Read, Stefan Schulz, André Fleißner
Sterols are vital components of eukaryotic cell membranes. Defects in sterol biosynthesis, which result in the accumulation of precursor molecules, are commonly associated with cellular disorders and disease. However, the effects of these sterol precursors on the metabolism, signaling, and behavior of cells are only poorly understood. In this study, we show that the accumulation of only ergosterol precursors with a conjugated double bond in their aliphatic side chain specifically disrupts cell-cell communication and fusion in the fungus Neurospora crassa Genetically identical germinating spores of this fungus undergo cell-cell fusion, thereby forming a highly interconnected supracellular network during colony initiation...
October 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Takashi Kikuma, Takayuki Tadokoro, Jun-Ichi Maruyama, Katsuhiko Kitamoto
Autophagy is a conserved process in eukaryotic cells for degradation of cellular proteins and organelles. In filamentous fungi, autophagic degradation of organelles such as peroxisomes, mitochondria, and nuclei occurs in basal cells after the prolonged culture, but its mechanism is not well understood. Here, we functionally analyzed the filamentous fungus Aspergillus oryzae AoAtg26, an ortholog of the sterol glucosyltransferase PpAtg26 involved in pexophagy in the yeast Pichia pastoris. Deletion of Aoatg26 caused a severe decrease in conidiation and aerial hyphae formation, which is typically observed in the autophagy-deficient A...
October 4, 2016: Bioscience, Biotechnology, and Biochemistry
Valérie Wattelet-Boyer, Lysiane Brocard, Kristoffer Jonsson, Nicolas Esnay, Jérôme Joubès, Frédéric Domergue, Sébastien Mongrand, Natasha Raikhel, Rishikesh P Bhalerao, Patrick Moreau, Yohann Boutté
The post-Golgi compartment trans-Golgi Network (TGN) is a central hub divided into multiple subdomains hosting distinct trafficking pathways, including polar delivery to apical membrane. Lipids such as sphingolipids and sterols have been implicated in polar trafficking from the TGN but the underlying mechanisms linking lipid composition to functional polar sorting at TGN subdomains remain unknown. Here we demonstrate that sphingolipids with α-hydroxylated acyl-chains of at least 24 carbon atoms are enriched in secretory vesicle subdomains of the TGN and are critical for de novo polar secretory sorting of the auxin carrier PIN2 to apical membrane of Arabidopsis root epithelial cells...
2016: Nature Communications
Fakhri Al-Bagdadi, Matthew J Young, James P Geaghan, Shaomian Yao, Humberto M Barona, Eduardo Martinez-Ceballos, Masami Yoshimura
It is estimated that 5.9% of all human deaths are attributable to alcohol consumption and that the harmful use of ethanol ranks among the top five risk factors for causing disease, disability, and death worldwide. Ethanol is known to disrupt phospholipid packing and promote membrane hemifusion at lipid bilayers. With the exception of mitochondria involved in hormone synthesis, the sterol content of mitochondrial membranes is low. As membranes that are low in cholesterol have increased membrane fluidity and are the most easily disordered by ethanol, we hypothesize that mitochondria are sensitive targets for ethanol damage...
September 28, 2016: Ultrastructural Pathology
J N Valitova, A G Sulkarnayeva, F V Minibayeva
Sterols, which are isoprenoid derivatives, are structural components of biological membranes. Special attention is now being given not only to their structure and function, but also to their regulatory roles in plants. Plant sterols have diverse composition; they exist as free sterols, sterol esters with higher fatty acids, sterol glycosides, and acylsterol glycosides, which are absent in animal cells. This diversity of types of phytosterols determines a wide spectrum of functions they play in plant life. Sterols are precursors of a group of plant hormones, the brassinosteroids, which regulate plant growth and development...
August 2016: Biochemistry. Biokhimii︠a︡
Alexandra Konecna, Nora Toth Hervay, Martin Valachovic, Yvetta Gbelska
The ERG6 gene encodes a S-adenosylmethionine dependent sterol C-24 methyltransferase in the ergosterol biosynthetic pathway. In this work we report the results of functional analysis of the Kluyveromyces lactis ERG6 gene. We cloned the KlERG6 gene, which was able to complement the erg6Δ mutation both in K. lactis and Saccharomyces cerevisiae. The lack of ergosterol in the Klerg6 deletion mutant was accompanied with increased expression of genes encoding last steps of ergosterol biosynthesis pathway as well as the KlPDR5 gene encoding an ABC transporter...
September 26, 2016: Yeast
Duhita G Sant, Santosh G Tupe, Chepuri V Ramana, Mukund V Deshpande
Increase in invasive fungal infections over past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armory includes very few effective drugs like Amphotericin B, new generation azoles including voriconazole and posaconazole, echinocandins like caspofungin, micafungin, to name a few. Azole class of antifungals which target fungal cell membrane are first choice of treatment for many years because of their effectiveness. As fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during last few years...
September 26, 2016: Journal of Applied Microbiology
Maria Ricci, Rosario Oliva, Pompea Del Vecchio, Marco Paolantoni, Assunta Morresi, Paola Sassi
Dimethyl sulfoxide (DMSO) is a universal solvent widely used in many fields, from basic research to industrial applications. At low concentration, it is the most important cryoprotectant agent against cellular damage caused during a freeze-thaw cycle. Although the effects of this cosolvent on the physico-chemical properties of a lipid bilayer have been extensively studied with both in vitro and in vivo experiments, the molecular mechanism of cryopreservation is not completely understood. Cholesterol (Chol) represents one of the essential cell membrane component and is fundamental to maintain the integrity and fluidity of the membrane...
September 21, 2016: Biochimica et Biophysica Acta
Rong Shuang, Xu Rui, Li Wenfang
As the aging of the world's population is becoming increasingly serious, dementia-related diseases have become a hot topic in public health research. In recent years, human epidemiological studies have focused on lipid metabolism disorders and dementia. The efficacy of phytosterol intake as a cholesterol-lowering agent has been demonstrated. Phytosterols directly serve as ligands of the nuclear receptors, peroxisome proliferator-activated receptors (PPARs), activating Sirtuin 1 (SIRT-1), which are involved in the regulation of lipid metabolism and the pathogenesis of dementia...
September 23, 2016: Plant Foods for Human Nutrition
Azucena Pérez-Cañamás, Sara Sarroca, Carolina Melero-Jerez, David Porquet, Joan Sansa, Shira Knafo, Jose A Esteban, Coral Sanfeliu, Maria Dolores Ledesma
Cholesterol reduction at the neuronal plasma membrane has been related to age-dependent cognitive decline. We have used senescent-accelerated mice strain 8 (SAMP8), an animal model for aging, to examine the association between cholesterol loss and cognitive impairment and to test strategies to revert this process. We show that the hippocampus of SAMP8 mice presents reduced cholesterol levels and enhanced amount of its degrading enzyme Cyp46A1 (Cyp46) already at 6 months of age. Cholesterol loss accounts for the impaired long-term potentiation in these mice...
August 20, 2016: Neurobiology of Aging
Wojciech Grudzinski, Joanna Sagan, Renata Welc, Rafal Luchowski, Wieslaw I Gruszecki
Amphotericin B is a popular antifungal antibiotic, a gold standard in treatment of systemic mycotic infections, due to its high effectiveness. On the other hand, applicability of the drug is limited by its considerable toxicity to patients. Biomembranes are a primary target of physiological activity of amphotericin B and both the pharmacologically desired and toxic side effects of the drug relay on its molecular organization in the lipid phase. In the present work, molecular organization, localization and orientation of amphotericin B, in a single lipid bilayer system, was analysed simultaneously, thanks to application of a confocal fluorescence lifetime imaging microscopy of giant unilamellar vesicles...
2016: Scientific Reports
Roman Sandor, Christophe Der, Kevin Grosjean, Iulia Anca, Elodie Noirot, Nathalie Leborgne-Castel, Jan Lochman, Françoise Simon-Plas, Patricia Gerbeau-Pissot
Although plants are exposed to a great number of pathogens, they usually defend themselves by triggering mechanisms able to limit disease development. Alongside signalling events common to most such incompatible interactions, modifications of plasma membrane (PM) physical properties could be new players in the cell transduction cascade. Different pairs of elicitors (cryptogein, oligogalacturonides, and flagellin) and plant cells (tobacco and Arabidopsis) were used to address the issue of possible modifications of plant PM biophysical properties induced by elicitors and their links to other events of the defence signalling cascade...
September 2016: Journal of Experimental Botany
Kimberly Cornelio, Rafael Atillo Espiritu, Yasuto Todokoro, Shinya Hanashima, Masanao Kinoshita, Nobuaki Matsumori, Michio Murata, Shinichi Nishimura, Hideaki Kakeya, Minoru Yoshida, Shigeki Matsunaga
Theonellamide A (TNM-A) is an antifungal bicyclic dodecapeptide isolated from a marine sponge Theonella sp. Previous studies have shown that TNM-A preferentially binds to 3β-hydroxysterol-containing membranes and disrupts membrane integrity. In this study, several (1)H NMR-based experiments were performed to investigate the interaction mode of TNM-A with model membranes. First, the aggregation propensities of TNM-A were examined using diffusion ordered spectroscopy; the results indicate that TNM-A tends to form oligomeric aggregates of 2-9 molecules (depending on peptide concentration) in an aqueous environment, and this aggregation potentially influences the membrane-disrupting activity of the peptide...
November 1, 2016: Bioorganic & Medicinal Chemistry
N D'Avanzo
The lipid landscapes of cellular membranes are complex and dynamic, are tissue dependent, and can change with the age and the development of a variety of diseases. Researchers are now gaining new appreciation for the regulation of ion channel proteins by the membrane lipids in which they are embedded. Thus, as membrane lipids change, for example, during the development of disease, it is likely that the ionic currents that conduct through the ion channels embedded in these membranes will also be altered. This chapter provides an overview of the complex regulation of prokaryotic and eukaryotic voltage-dependent sodium (Nav) channels by fatty acids, sterols, glycerophospholipids, sphingolipids, and cannabinoids...
2016: Current Topics in Membranes
Whasun Lim, Changwon Yang, Fuller W Bazer, Gwonhwa Song
Luteolin is a natural compound known for its anticancer effects on various human cancers by regulating signal transduction cascades. However, the effects of luteolin on human placental choriocarcinoma are not known. Results of the present study revealed that luteolin decreased viability of JAR and JEG-3 cells, which are valuable placental models, in a dose-dependent manner, and it induced apoptosis and loss of mitochondrial membrane potential in JAR and JEG-3 cells. The results also suggested that the PI3K/AKT pathway was inhibited by luteolin treatment of JAR and JEG-3 cells in a dose- and time-dependent manner...
October 2016: Biology of Reproduction
Peter D Nagy
Plant positive-strand (+)RNA viruses are intracellular infectious agents that reorganize subcellular membranes and rewire the cellular metabolism of host cells to achieve viral replication in elaborate replication compartments. This review describes the viral replication process based on tombusviruses, highlighting common strategies with other plant and animal viruses. Overall, the works on Tomato bushy stunt virus (TBSV) have revealed intriguing and complex functions of co-opted cellular translation factors, heat shock proteins, DEAD-box helicases, lipid transfer proteins, and membrane-deforming proteins in virus replication...
September 29, 2016: Annual Review of Virology
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