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Membrane Sterols

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https://www.readbyqxmd.com/read/29348169/lipid-mediated-signals-that-regulate-mitochondrial-biology
#1
Jason R Nielson, Jared P Rutter
For decades, lipids were assumed to fulfill roles only in energy storage and membrane structure. Recent studies have discovered critical roles for phospholipids, sphingolipids, and sterols in many cellular pathways, including cell signaling and transcriptional regulation. Frequently, lipids from these various classes work together to achieve defined cellular outcomes. Specific mitochondrial lipids are critical for proper assembly of the electron transport chain complexes and for effective responses to mitochondrial damage, including maintenance of mitochondrial protein homeostasis, regulation of mitophagy, and induction of apoptosis...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348118/targeted-deletion-of-adipocyte-abca1-atp-binding-cassette-transporter-a1-impairs-diet-induced-obesity
#2
Helen Cuffe, Mingxia Liu, Chia-Chi C Key, Elena Boudyguina, Janet K Sawyer, Allison Weckerle, Alexander Bashore, Susan K Fried, Soonkyu Chung, John S Parks
OBJECTIVE: Adipose tissue cholesterol increases with adipocyte triglyceride content and size during development of obesity. However, how adipocyte cholesterol affects adipocyte function is poorly understood. The aim of this study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP-binding cassette transporter A1), on adipose tissue function during diet-induced obesity. APPROACH AND RESULTS: Adiponectin Cre recombinase transgenic mice were crossed with Abca1flox/flox mice to generate ASKO (adipocyte-specific Abca1 knockout) mice...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29339490/structural-basis-of-sterol-recognition-and-nonvesicular-transport-by-lipid-transfer-proteins-anchored-at-membrane-contact-sites
#3
Junsen Tong, Mohammad Kawsar Manik, Young Jun Im
Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29319811/identification-of-a-consensus-motif-in-erg28p-required-for-c-4-demethylation-in-yeast-ergosterol-biosynthesis-based-on-mutation-analysis
#4
Xia Ke, Xiao-Yuan Xia, Ren-Chao Zheng, Yu-Guo Zheng
The Erg28p protein is localized to the endoplasmic reticulum (ER), where it acts as a scaffold to tether the C-4 demethylase complex involved in the sterol biosynthesis pathway of Saccharomyces cerevisiae. However, due to the challenges involved in characterizing the interactions of membrane proteins, the precise region of Erg28p that is responsible for the assembly of this enzyme complex remains unknown. To address this question, mutants with serial truncations in the C-terminus of Erg28p were constructed based on a topology prediction of its transmembrane domain...
January 8, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29305832/all-n-3-pufa-are-not-the-same-md-simulations-reveal-differences-in-membrane-organization-for-epa-dha-and-dpa
#5
Xiaoling Leng, Jacob J Kinnun, Andres T Cavazos, Samuel W Canner, Saame Raza Shaikh, Scott E Feller, Stephen R Wassall
Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers...
January 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29295605/discrimination-of-stereoisomers-by-their-enantioselective-interactions-with-chiral-cholesterol-containing-membranes
#6
Hironori Tsuchiya, Maki Mizogami
Discrimination between enantiomers is an important subject in medicinal and biological chemistry because they exhibit markedly different bioactivity and toxicity. Although stereoisomers should vary in the mechanistic interactions with chiral targets, their discrimination associated with the mode of action on membrane lipids is scarce. The aim of this study is to reveal whether enantiomers selectively act on chiral lipid membranes. Different classes of stereoisomers were subjected at 5-200 μM to reactions with biomimetic phospholipid membranes containing ~40 mol % cholesterol to endow the lipid bilayers with chirality and their membrane interactions were comparatively evaluated by measuring fluorescence polarization...
December 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29288621/arabidopsis-acyl-coa-binding-protein1-interacts-with-sterol-c4-methyl-oxidase1-2-to-modulate-gene-expression-of-homeodomain-leucine-zipper-iv-transcription-factors
#7
Shiu-Cheung Lung, Pan Liao, Edward C Yeung, An-Shan Hsiao, Yan Xue, Mee-Len Chye
Fatty acids (FAs) and sterols constitute building blocks of eukaryotic membranes and lipid signals. Co-regulation of FA and sterol synthesis is mediated by sterol regulatory element-binding proteins in animals but remains elusive in plants. We reported recently that Arabidopsis ACYL-COA-BINDING PROTEIN1 (ACBP1) modulates sterol synthesis via protein-protein interaction with STEROL C4-METHYL OXIDASE1-1 (SMO1-1). Herein, ACBP1 was demonstrated to co-express and interact with SMO1-2 by yeast two-hybrid, co-localization, pull-down, co-immunoprecipitation and β-glucuronidase assays...
December 30, 2017: New Phytologist
https://www.readbyqxmd.com/read/29287714/fluconazole-inhibits-the-cellular-ergosterol-synthesis-to-confer-synergism-to-berberine-against-yeast-cells
#8
Zhanju Yang, Qiao Wang, Ke Ma, Ping Shi, Wenbin Liu, Zhiwei Huang
OBJECTIVES: The study aims to explore the synergistically antifungal mechanism of fluconazole and berberine. METHODS: Biochemical and genetic analysis was performed to investigate the probable antifungal role of the combined use of berberine and fluconazole in Saccharomyces cerevisiae, a typical fungal cell model. RESULTS: Fluconazole led to an elevated cell membrane permeability in the wild type yeast BY4741, similar as the sterol synthesis deficient strains erg2Δ and erg6Δ...
December 26, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29284029/cyp51-is-an-essential-drug-target-for-the-treatment-of-primary-amoebic-meningoencephalitis-pam
#9
Anjan Debnath, Claudia M Calvet, Gareth Jennings, Wenxu Zhou, Alexander Aksenov, Madeline R Luth, Ruben Abagyan, W David Nes, James H McKerrow, Larissa M Podust
Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases...
December 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29282820/ergosterol-is-mainly-located-in-the-cytoplasmic-leaflet-of-the-yeast-plasma-membrane
#10
Lukasz M Solanko, David P Sullivan, Yves Y Sere, Maria Szomek, Anita Lunding, Katarzyna A Solanko, Azra Pizovic, Lyubomir D Stanchev, Thomas Günther Pomorski, Anant K Menon, Daniel Wüstner
Transbilayer lipid asymmetry is a fundamental characteristic of the eukaryotic cell plasma membrane (PM). While PM phospholipid asymmetry is well documented, the transbilayer distribution of PM sterols such as mammalian cholesterol and yeast ergosterol is not reliably known. We now report that sterols are asymmetrically distributed across the yeast PM, with the majority (~80%) located in the cytoplasmic leaflet. By exploiting the sterol-auxotrophic hem1Δ yeast strain we obtained cells in which endogenous ergosterol was quantitatively replaced with dehydroergosterol (DHE), a closely related fluorescent sterol that functionally and accurately substitutes for ergosterol in vivo...
December 28, 2017: Traffic
https://www.readbyqxmd.com/read/29274338/structural-insights-into-a-start-like-domain-in-lam4-and-its-interaction-with-sterol-ligands
#11
Alberto T Gatta, Andrea C Sauerwein, Anastasia Zhuravleva, Tim P Levine, Stephen Matthews
Sterols are essential components of cellular membranes and shape their biophysical properties. The recently discovered family of Lipid transfer proteins Anchored at Membrane contact sites (LAMs) has been suggested to carry out intracellular sterol traffic using StART-like domains. Here, we studied the second StART-like domain of Lam4p from S. cerevisiae by NMR. We show that NMR data are consistent with the StART-like domain structure, and that several functionally important regions within the domain exhibit significant conformational dynamics...
December 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29262315/cell-autonomous-control-of-neuronal-dendrite-expansion-via-the-fatty-acid-synthesis-regulator-srebp
#12
Anna B Ziegler, Christoph Thiele, Federico Tenedini, Mélisande Richard, Philipp Leyendecker, Astrid Hoermann, Peter Soba, Gaia Tavosanis
During differentiation, neurons require a high lipid supply for membrane formation as they elaborate complex dendritic morphologies. While glia-derived lipids support neuronal growth during development, the importance of cell-autonomous lipid production for dendrite formation has been unclear. Using Drosophila larva dendritic arborization (da) neurons, we show that dendrite expansion relies on cell-autonomous fatty acid production. The nociceptive class four (CIV) da neurons form particularly large space-filling dendrites...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29249985/lysosomal-and-mitochondrial-liaisons-in-niemann-pick-disease
#13
REVIEW
Sandra Torres, Elisa Balboa, Silvana Zanlungo, Carlos Enrich, Carmen Garcia-Ruiz, Jose C Fernandez-Checa
Lysosomal storage disorders (LSD) are characterized by the accumulation of diverse lipid species in lysosomes. Niemann-Pick type A/B (NPA/B) and type C diseases Niemann-Pick type C (NPC) are progressive LSD caused by loss of function of distinct lysosomal-residing proteins, acid sphingomyelinase and NPC1, respectively. While the primary cause of these diseases differs, both share common biochemical features, including the accumulation of sphingolipids and cholesterol, predominantly in endolysosomes. Besides these alterations in lysosomal homeostasis and function due to accumulation of specific lipid species, the lysosomal functional defects can have far-reaching consequences, disrupting intracellular trafficking of sterols, lipids and calcium through membrane contact sites (MCS) of apposed compartments...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29243365/vitamin-a-coupled-liposome-system-targeting-free-cholesterol-accumulation-in-hepatic-stellate-cells-offers-a-beneficial-therapeutic-strategy-for-liver-fibrosis
#14
Hirotaka Furuhashi, Kengo Tomita, Toshiaki Teratani, Motonori Shimizu, Makoto Nishikawa, Masaaki Higashiyama, Takeshi Takajo, Kazuhiko Shirakabe, Koji Maruta, Yoshikiyo Okada, Chie Kurihara, Chikako Watanabe, Shunsuke Komoto, Suefumi Aosasa, Shigeaki Nagao, Junji Yamamoto, Soichiro Miura, Ryota Hokari
AIM: Liver fibrosis is a life-threatening disorder for which no approved therapy is available. Recently, we reported that mouse hepatic stellate cell (HSC) activation increased free cholesterol (FC) accumulation partly by enhancing signaling via sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-β (TGFβ)-induced activation in a 'vicious cycle' of liver fibrosis. METHODS: Human HSCs were isolated from surgical liver specimens from the control patients and patients with liver fibrosis...
December 15, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29225604/transcriptional-regulation-of-t-cell-lipid-metabolism-implications-for-plasma-membrane-lipid-rafts-and-t-cell-function
#15
REVIEW
George A Robinson, Kirsty E Waddington, Ines Pineda-Torra, Elizabeth C Jury
It is well established that cholesterol and glycosphingolipids are enriched in the plasma membrane (PM) and form signaling platforms called lipid rafts, essential for T-cell activation and function. Moreover, changes in PM lipid composition affect the biophysical properties of lipid rafts and have a role in defining functional T-cell phenotypes. Here, we review the role of transcriptional regulators of lipid metabolism including liver X receptors α/β, peroxisome proliferator-activated receptor γ, estrogen receptors α/β (ERα/β), and sterol regulatory element-binding proteins in T-cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29223352/atp-binding-cassette-transporter-2-abca2-as-a-therapeutic-target
#16
REVIEW
Warren Davis, Kenneth D Tew
The ATP binding cassette transporter ABCA2 is primarily an endolysosomal membrane protein that demonstrates pleiotropic functionalities, coalescing around the maintenance of homeostasis of sterols, sphingolipids and cholesterol. It is most highly expressed in brain tissue and ABCA2 knockout mice express neurological defects consistent with aberrant myelination. Increased expression of the transporter has been linked with resistance to cancer drugs, particularly those possessing a steroid backbone and gene expression (in concert with other genes involved in cholesterol metabolism) was found to be regulated by sterols...
December 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29189433/transintestinal-cholesterol-excretion-in-humans
#17
Laurens F Reeskamp, Emma C E Meessen, Albert K Groen
PURPOSE OF REVIEW: To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. RECENT FINDINGS: TICE is the net effect of cholesterol excretion by the enterocyte into the intestinal lumen and is the balance between input and output fluxes through the enterocytes. These fluxes are: cholesterol excretion into the intestinal lumen mainly via ATP-binding cassette (ABC) G5/8, cholesterol absorption from the intestine by Niemann-Pick C1 like protein 1, the uptake of plasma lipoproteins by enterocytes at the basolateral membrane, and the excretion of cholesterol in chylomicrons into the lymph...
February 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29182278/understanding-how-sterols-regulate-membrane-remodeling-in-supported-lipid-bilayers
#18
Lisa Margaret Kawakami, Bo Kyeong Yoon, Joshua Alexander Jackman, Wolfgang Knoll, Paul S Weiss, Nam-Joon Cho
The addition of single-chain lipid amphiphiles such as antimicrobial fatty acids and monoglycerides to confined, two-dimensional phospholipid bilayers can trigger the formation of three-dimensional membrane morphologies as a passive means to regulate stress. To date, relevant experimental studies have been conducted using pure phospholipid compositions and extending such insights to more complex, biologically relevant lipid compositions that include phospholipids and sterols is warranted because sterols are important biological mediators of membrane stress relaxation...
November 28, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29173820/orp-mediated-er-contact-with-endocytic-sites-facilitates-actin-polymerization
#19
Javier Encinar Del Dedo, Fatima-Zahra Idrissi, Isabel María Fernandez-Golbano, Patricia Garcia, Elena Rebollo, Marek K Krzyzanowski, Helga Grötsch, Maria Isabel Geli
Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid transport and work as lipid sensors in the context of many cellular tasks, but the determinants of their distinct localization and function are not understood. Here, we demonstrate that the yeast endocytic invaginations associate with the ER and that this association specifically requires the ORPs Osh2 and Osh3, which bridge the endocytic myosin-I Myo5 to the ER integral-membrane VAMP-associated protein (VAP) Scs2...
November 17, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29169746/simulations-of-simple-bovine-and-homo-sapiens-outer-cortex-ocular-lens-membrane-models-with-a-majority-concentration-of-cholesterol
#20
Mark Adams, Eric Wang, Xiaohong Zhuang, Jeffery B Klauda
The lipid composition of bovine and human ocular lens membranes has been probed, and a variety of lipids have been found including phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and cholesterol (CHOL) with cholesterol being present in particularly high concentrations. In this study, we use the all-atom CHARMM36 force field to simulate binary, ternary, and quaternary mixtures as models of the ocular lens. High concentration of cholesterol, in combination with different and varying diversity of phospholipids (PL) and sphingolipids (SL), affect the structure of the ocular lens lipid bilayer...
November 20, 2017: Biochimica et Biophysica Acta
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