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Membrane Sterols

Rosa de la Torre Noetzel, Ana Z Miller, José M de la Rosa, Claudia Pacelli, Silvano Onofri, Leopoldo García Sancho, Beatriz Cubero, Andreas Lorek, David Wolter, Jean P de Vera
Lichens are extremely resistant organisms that colonize harsh climatic areas, some of them defined as "Mars-analog sites." There still remain many unsolved questions as to how lichens survive under such extreme conditions. Several studies have been performed to test the resistance of various lichen species under space and in simulated Mars-like conditions. The results led to the proposal that Circinaria gyrosa (Lecanoromycetes, Ascomycota) is one of the most durable astrobiological model lichens. However, although C ...
2018: Frontiers in Microbiology
Antonietta Pietrangelo, Neale D Ridgway
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation...
March 13, 2018: Cellular and Molecular Life Sciences: CMLS
Melissa Conte, Josselin Lupette, Khawla Seddiki, Coline Meï, Lina J Dolch, Valerie Gros, Caroline Barette, Fabrice Rébeillé, Juliette Jouhet, Eric Marechal
Microalgae are a promising feedstock for the production of triacylglycerol (TAG) for a variety of potential applications, ranging from food and human health to biofuels and green chemistry. However, obtaining high TAG yields is challenging. A phenotypic assay for accumulation of oil droplets was developed to screen a library of 1,200 drugs, annotated with pharmacology information, to select compounds that trigger TAG accumulation in the diatom Phaeodactylum. Using this screen, we identified 34 molecules acting in a dose-dependent manner...
March 13, 2018: Plant Physiology
Stephen R Brand, Thorsten P Degenhardt, Karen Person, Jack D Sobel, Paul Nyirjesy, Robert J Schotzinger, Amir Tavakkol
BACKGROUND: Lanosterol demethylase (CYP51), is an enzyme essential for fungal growth, and catalyzes an early step in the biosynthetic pathway of ergosterol, a sterol required for fungal cell membrane formation and integrity. CYP51 is the molecular target of the class of drugs referred to as 'azole antifungals.' VT-1161 is a novel, oral, selective inhibitor of fungal CYP51, and is being developed for the treatment of recurrent vulvovaginal candidiasis. OBJECTIVE: We evaluated the efficacy and safety of 4 dosing regimens of oral VT-1161 compared to placebo in women with recurrent vulvovaginal candidiasis, defined as at least 3 symptomatic episodes of acute vulvovaginal candidiasis within a 12-month period...
March 10, 2018: American Journal of Obstetrics and Gynecology
Ananda Kafle, Takeshi Misono, Avinash Bhadani, Masaaki Akamatsu, Kenichi Sakai, Chihiro Kaise, Teruhisa Kaneko, Hideki Sakai
We have studied the phase behavior of distearoylphosphatidylcholine (DSPC) in the presence of sodium β-sitosteryl sulfate (PSO4 ). PSO4 was found to induce sterol-rich and sterol-poor domains in the DSPC membrane. These two domains constitute a fluid, liquid ordered (Lo ) phase and a gel (Lβ ) phase. PSO4 was less miscible in DSPC than in a dipalmitoylphosphatidylcholine (DPPC) membrane, as evidenced by its tendency to separate from the bilayer at a concentration of 50 mol%. This lack of miscibility was attributed to the greater van der Waals forces between the PC hydrocarbon chains...
March 9, 2018: Journal of Oleo Science
Tiange Li, Jing Gao, Min Du, Jiajia Song, Xueying Mao
Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many health benefits. The aim of the current study was to investigate whether MFGM could prevent obesity through inhibiting adipogenesis and promoting brown remodeling of white adipose tissue (WAT) in mice fed with high-fat diet. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD plus MFGM at 100 mg/kg BW, 200 mg/kg BW or 400 mg/kg BW for 8 weeks. Results showed that MFGM suppressed body weight gain induced by HFD, reduced white adipose tissue (WAT) mass accompanied with the decrease in adipocyte sizes...
March 9, 2018: Nutrients
Garima Jaipuria, Tina Ukmar-Godec, Markus Zweckstetter
Experimental evidence for a direct role of lipids in determining the structure, dynamics, and function of membrane proteins leads to the term 'functional lipids'. In particular, the sterol molecule cholesterol modulates the activity of many membrane proteins. The precise nature of cholesterol-binding sites and the consequences of modulation of local membrane micro-viscosity by cholesterol, however, is often unknown. Here, we review the current knowledge of the interaction of cholesterol with transmembrane proteins, with a special focus on structural aspects of the interaction derived from nuclear magnetic resonance approaches...
March 8, 2018: Cellular and Molecular Life Sciences: CMLS
I N Goronzy, R J Rawle, S G Boxer, P M Kasson
Influenza virus infects cells by binding to sialylated glycans on the cell surface. While the chemical structure of these glycans determines hemagglutinin-glycan binding affinity, bimolecular affinities are weak, so binding is avidity-dominated and driven by multivalent interactions. Here, we show that membrane spatial organization can control viral binding. Using single-virus fluorescence microscopy, we demonstrate that the sterol composition of the target membrane enhances viral binding avidity in a dose-dependent manner...
February 28, 2018: Chemical Science
M Modzel, K A Solanko, M Szomek, S K Hansen, A Dupont, L J Nåbo, J Kongsted, D Wüstner
Analysis of intracellular cholesterol transport by fluorescence microscopy requires suitable fluorescent analogues of cholesterol. Most existing cholesterol analogues contain lipophilic dyes which can compromise the sterol properties in membranes. An alternative strategy is to introduce additional double bonds into the sterol ring system resulting in intrinsic fluorescence, while at the same time keeping the cholesterol-like properties of the analogues. Existing polyene sterols, such as dehydroergosterol (DHE) or cholestatrienol (CTL), however, contain only three double bonds and suffer from low brightness, significant photobleaching and excitation/emission in the ultraviolet region...
March 8, 2018: Journal of Microscopy
Quan-Zhen Lv, Yu-Lin Qin, Lan Yan, Liang Wang, Chuyue Zhang, Yuan-Ying Jiang
Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the ORF19.273 in Candida albicans , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole, nsg2 Δ/Δ mutants are seriously damaged in the integrity and functions of cell membranes with a decrease of ergosterol ratio and an increase of both obtusifoliol and 14α-methylfecosterol ratio...
2018: Frontiers in Microbiology
Bing Han, Ning Yang, Hai Pu, Tai Wang
Cell polarity is essential for generating diverse cell functions. The underlying mechanisms of how a cell establishes, maintains and changes its polarity are poorly understood. Recently, sterol-rich membrane microdomains are found to be associated with these processes. However, both its exact characteristics and importance are still unclear. Here we show microdomains change dynamically in developing and germinating rice pollen with selective enrichment in the aperture and the tip of newly-born pollen tubes by use of the sterol-specific probe filipin...
March 6, 2018: Journal of Proteome Research
Holly Bennett, James J Bell, Simon K Davy, Nicole S Webster, David S Francis
Ocean warming (OW) and ocean acidification (OA) are threatening coral reef ecosystems, with a bleak future forecast for reef-building corals, which are already experiencing global declines in abundance. In contrast, many coral reef sponge species are able to tolerate climate change conditions projected for 2100. To increase our understanding of the mechanisms underpinning this tolerance, we explored the lipid and fatty acid (FA) composition of four sponge species with differing sensitivities to climate change, experimentally exposed to OW and OA levels predicted for 2100, under two CO2 Representative Concentration Pathways (RCPs)...
March 5, 2018: Global Change Biology
Russell A DeBose-Boyd, Jin Ye
Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that activate genes encoding enzymes required for synthesis of cholesterol and unsaturated fatty acids. SREBPs are controlled by multiple mechanisms at the level of mRNA synthesis, proteolytic activation, and transcriptional activity. In this review, we summarize the recent findings that contribute to the current understanding of the regulation of SREBPs and their physiologic roles in maintenance of lipid homeostasis, insulin signaling, innate immunity, and cancer development...
February 27, 2018: Trends in Biochemical Sciences
Siqi Tian, Akinori Ohta, Hiroyuki Horiuchi, Ryouichi Fukuda
Sterols are present in eukaryotic membranes and significantly affect membrane fluidity, permeability, and microdomain formation. They are synthesized in the endoplasmic reticulum (ER) and transported to other organelles and the plasma membrane. Sterols play important roles in the biogenesis and maintenance of mitochondrial membranes. However, the mechanisms underlying ER-to-mitochondrion sterol transport remain to be identified. Here, using purified yeast membrane fractions enriched in ER and mitochondria, we show that the oxysterol-binding protein homologs encoded by the OSH genes in the yeast Saccharomyces cerevisiae mediate sterol transport from the ER to mitochondria...
February 27, 2018: Journal of Biological Chemistry
Marina Besprozvannaya, Eamonn Dickson, Hao Li, Kenneth S Ginburg, Donald M Bers, Johan Auwerx, Jodi Nunnari
Endoplasmic reticulum (ER) membrane contact sites (MCSs) are crucial regulatory hubs in cells, playing roles in signaling, organelle dynamics, and ion and lipid homeostasis. Previous work demonstrated that the highly conserved yeast Ltc/Lam sterol transporters localize and function at ER MCSs. Our analysis of the human family members, GRAMD1a and GRAMD2a, demonstrates that they are ER-PM MCS proteins, which mark separate regions of the plasma membrane (PM) and perform distinct functions in vivo. GRAMD2a, but not GRAMD1a, co-localizes with the E-Syt2/3 tethers at ER-PM contacts in a PIP lipid-dependent manner and pre-marks the subset of PI(4,5)P2-enriched ER-PM MCSs utilized for STIM1 recruitment...
February 22, 2018: ELife
Florian A Horenkamp, Diana P Valverde, Jodi Nunnari, Karin M Reinisch
Lipid transport proteins at membrane contact sites, where two organelles are closely apposed, play key roles in trafficking lipids between cellular compartments while distinct membrane compositions for each organelle are maintained. Understanding the mechanisms underlying non-vesicular lipid trafficking requires characterization of the lipid transporters residing at contact sites. Here, we show that the mammalian proteins in the lipid transfer proteins anchored at a membrane contact site (LAM) family, called GRAMD1a-c, transfer sterols with similar efficiency as the yeast orthologues, which have known roles in sterol transport...
February 21, 2018: EMBO Journal
Julian-Alexander Jentsch, Irene Kiburu, Kalpana Pandey, Michael Timme, Trudy Ramlall, Bodo Levkau, Jin Wu, David Eliezer, Olga Boudker, Anant K Menon
The StARkin superfamily comprises proteins with steroidogenic acute regulatory protein related lipid transfer (StART) domains that are implicated in intracellular, non-vesicular lipid transport. A new family of membrane-anchored StARkins was recently identified, including six members Lam1-Lam6 in the yeast Saccharomyces cerevisiae. Lam1-Lam4 are anchored to the endoplasmic reticulum (ER) membrane at sites where the ER is tethered to the plasma membrane, and proposed to be involved in sterol homeostasis in yeast...
February 20, 2018: Journal of Biological Chemistry
Emily G Armitage, Amjed Q I Alqaisi, Joanna Godzien, Imanol Peña, Alison J Mbekeani, Vanesa Alsonso-Herranz, Ángeles López-Gonzálvez, Julio Martín, Raquel Gabarro, Paul W Denny, Michael P Barrett, Coral Barbas
With the World Health Organization reporting over 30,000 deaths and 200-400,000 new cases annually, visceral Leishmania sis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for Leishmania sis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new, more successful treatments for Leishmania sis...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Koji Mikami, Meiko Ito, Kensuke Taya, Ikuya Kishimoto, Takuya Kobayashi, Yutaka Itabashi, Ryusuke Tanaka
In the filamentous brown alga Ectocarpus siliculosus, male and female sex is expressed during the haploid parthenosporophyte phase of the life cycle. Here, we found that male parthenosporophytes displayed thermotolerance whereas female specimens displayed severely reduced viability at 25 °C and 28 °C. Profiling of polyunsaturated fatty acids showed that n-3 and n-6 were the predominant species in male and female parthenosporophytes, respectively, and that the n-3/n-6 fatty acid ratio was not affected by a temperature change...
February 10, 2018: Marine Environmental Research
Brittany J Belin, Nicolas Busset, Eric Giraud, Antonio Molinaro, Alba Silipo, Dianne K Newman
Lipid research represents a frontier for microbiology, as showcased by hopanoid lipids. Hopanoids, which resemble sterols and are found in the membranes of diverse bacteria, have left an extensive molecular fossil record. They were first discovered by petroleum geologists. Today, hopanoid-producing bacteria remain abundant in various ecosystems, such as the rhizosphere. Recently, great progress has been made in our understanding of hopanoid biosynthesis, facilitated in part by technical advances in lipid identification and quantification...
February 19, 2018: Nature Reviews. Microbiology
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