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  1 / 7499 MEDLINE  
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[PMID]:29031613
[Au] Autor:Majd H; King MS; Smith AC; Kunji ERS
[Ad] Endereço:Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
[Ti] Título:Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.
[So] Source:Biochim Biophys Acta;1859(1):1-7, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes.
[Mh] Termos MeSH primário: Proteínas de Transporte de Ânions
Ácido Cítrico/metabolismo
Simulação por Computador
Dolicol
Proteínas Mitocondriais
Modelos Biológicos
Mutação de Sentido Incorreto
Esteróis
Ubiquinona
[Mh] Termos MeSH secundário: Proteínas de Transporte de Ânions/química
Proteínas de Transporte de Ânions/genética
Proteínas de Transporte de Ânions/metabolismo
Transporte Biológico Ativo/genética
Encefalopatias Metabólicas Congênitas/enzimologia
Encefalopatias Metabólicas Congênitas/genética
Domínio Catalítico
Dolicol/biossíntese
Dolicol/química
Dolicol/genética
Seres Humanos
Proteínas Mitocondriais/química
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Esteróis/biossíntese
Esteróis/química
Esteróis/metabolismo
Ubiquinona/biossíntese
Ubiquinona/química
Ubiquinona/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Mitochondrial Proteins); 0 (Slc25a1 protein, human); 0 (Sterols); 1339-63-5 (Ubiquinone); 2067-66-5 (Dolichol); 2968PHW8QP (Citric Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


  2 / 7499 MEDLINE  
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[PMID]:28480734
[Au] Autor:Kumar A; Chand G; Agnihotri VK
[Ad] Endereço:a Academy of Scientific and Innovative Research , CSIR-Institute of Himalayan Bioresource Technology , Palampur , India.
[Ti] Título:A new oxo-sterol derivative from the rhizomes of Costus speciosus.
[So] Source:Nat Prod Res;32(1):18-22, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chemical investigation of the rhizomes of Costus speciosus led to the isolation of a new compound, 22-ketocholesteryl palmitate (1) along with four known compounds, 24-methylenecycloartanol (2), cycloartanol (3), stigmasterol (4) and linoleic acid (5). The structure of new compound was characterised by extensive 1D-, 2D-NMR and mass spectrometry (GC-MS and HR-ESI-MS) techniques.
[Mh] Termos MeSH primário: Costus/química
Cetosteroides/química
Rizoma/química
Esteróis/química
[Mh] Termos MeSH secundário: Cromatografia Gasosa-Espectrometria de Massas
Ácido Linoleico/química
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Espectrometria de Massas por Ionização por Electrospray/métodos
Estigmasterol/química
Triterpenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (24-methylenecycloartenol); 0 (Ketosteroids); 0 (Sterols); 0 (Triterpenes); 99WUK5D0Y8 (Stigmasterol); 9KJL21T0QJ (Linoleic Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1324962


  3 / 7499 MEDLINE  
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[PMID]:29274338
[Au] Autor:Gatta AT; Sauerwein AC; Zhuravleva A; Levine TP; Matthews S
[Ad] Endereço:UCL Institute of Ophthalmology, Department of Cell Biology, 11-43 Bath Street, London EC1V 9EL, UK. Electronic address: alberto.gatta@crick.ac.uk.
[Ti] Título:Structural insights into a StART-like domain in Lam4 and its interaction with sterol ligands.
[So] Source:Biochem Biophys Res Commun;495(3):2270-2274, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. NMR titration experiments confirm sterol binding to the canonical sterol-binding site and suggest a role of membrane interactions on the thermodynamics and kinetics of sterol binding.
[Mh] Termos MeSH primário: Proteínas de Transporte/química
Proteínas de Transporte/ultraestrutura
Modelos Químicos
Simulação de Acoplamento Molecular
Esteróis/química
[Mh] Termos MeSH secundário: Sítios de Ligação
Ligantes
Ligação Proteica
Conformação Proteica
Domínios Proteicos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Ligands); 0 (Sterols); 0 (lipid transfer protein)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


  4 / 7499 MEDLINE  
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[PMID]:29284029
[Au] Autor:Debnath A; Calvet CM; Jennings G; Zhou W; Aksenov A; Luth MR; Abagyan R; Nes WD; McKerrow JH; Podust LM
[Ad] Endereço:Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
[Ti] Título:CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM).
[So] Source:PLoS Negl Trop Dis;11(12):e0006104, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
[Mh] Termos MeSH primário: Inibidores de 14-alfa Desmetilase/farmacologia
Amebicidas/farmacologia
Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico
Reposicionamento de Medicamentos
Naegleria fowleri/efeitos dos fármacos
Nitrilos/farmacologia
Piridinas/farmacologia
Triazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Antifúngicos/farmacologia
Proliferação Celular/efeitos dos fármacos
Infecções Protozoárias do Sistema Nervoso Central/mortalidade
Infecções Protozoárias do Sistema Nervoso Central/parasitologia
Modelos Animais de Doenças
Seres Humanos
Microscopia Eletrônica de Transmissão
Naegleria fowleri/ultraestrutura
Esterol 14-Desmetilase/metabolismo
Esteróis/biossíntese
Trofozoítos/efeitos dos fármacos
Trofozoítos/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (14-alpha Demethylase Inhibitors); 0 (Amebicides); 0 (Antifungal Agents); 0 (Nitriles); 0 (Pyridines); 0 (Sterols); 0 (Triazoles); 60UTO373KE (isavuconazole); 6TK1G07BHZ (posaconazole); EC 1.14.13.70 (Sterol 14-Demethylase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171229
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006104


  5 / 7499 MEDLINE  
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[PMID]:29281643
[Au] Autor:Calvet CM; Choi JY; Thomas D; Suzuki B; Hirata K; Lostracco-Johnson S; de Mesquita LB; Nogueira A; Meuser-Batista M; Silva TA; Siqueira-Neto JL; Roush WR; de Souza Pereira MC; McKerrow JH; Podust LM
[Ad] Endereço:Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
[Ti] Título:4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.
[So] Source:PLoS Negl Trop Dis;11(12):e0006132, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice. METHODOLOGY/PRINCIPAL FINDINGS: Both acute and chronic animal models infected with wild type or transgenic T. cruzi strains were evaluated. There was no evidence of toxicity in the 28-day dosing study of uninfected animals, as judged by the monitoring of multiple serum and histological parameters. In two acute models of Chagas disease, 9 and 12 drastically reduced parasitemia, increased survival of mice, and prevented liver and heart injury. None of the compounds produced long term sterile cure. In the less severe acute model using the transgenic CL-Brenner strain of T.cruzi, parasitemia relapsed upon drug withdrawal. In the chronic model, parasitemia fell to a background level and, as evidenced by the bioluminescence detection of T. cruzi expressing the red-shifted luciferase marker, mice remained negative for 4 weeks after drug withdrawal. Two immunosuppression cycles with cyclophosphamide were required to re-activate the parasites. Although no sterile cure was achieved, the suppression of parasitemia in acutely infected mice resulted in drastically reduced inflammation in the heart. CONCLUSIONS/SIGNIFICANCE: The positive outcomes achieved in the absence of sterile cure suggest that the target product profile in anti-Chagasic drug discovery should be revised in favor of safe re-administration of the medication during the lifespan of a Chagas disease patient. A medication that reduces parasite burden may halt or slow progression of cardiomyopathy and therefore improve both life expectancy and quality of life.
[Mh] Termos MeSH primário: Inibidores de 14-alfa Desmetilase/uso terapêutico
Doença de Chagas/tratamento farmacológico
Parasitemia/tratamento farmacológico
Pirimidinas/uso terapêutico
Tripanossomicidas/uso terapêutico
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Inibidores de 14-alfa Desmetilase/efeitos adversos
Animais
Doença de Chagas/parasitologia
Modelos Animais de Doenças
Descoberta de Drogas
Feminino
Coração/efeitos dos fármacos
Chumbo/química
Chumbo/uso terapêutico
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Miocárdio/patologia
Parasitemia/parasitologia
Pirimidinas/efeitos adversos
Esterol 14-Desmetilase/metabolismo
Esteróis/biossíntese
Tripanossomicidas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (14-alpha Demethylase Inhibitors); 0 (Pyrimidines); 0 (Sterols); 0 (Trypanocidal Agents); 2P299V784P (Lead); 591-54-8 (4-aminopyrimidine); EC 1.14.13.70 (Sterol 14-Demethylase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006132


  6 / 7499 MEDLINE  
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[PMID]:28461680
[Au] Autor:Kohlwein SD
[Ad] Endereço:Institute of Molecular Biosciences, University of Graz, BioTechMed Graz, 8010 Graz, Austria sepp.kohlwein@uni-graz.at.
[Ti] Título:Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor.
[So] Source:Cold Spring Harb Protoc;2017(5):pdb.top078956, 2017 May 01.
[Is] ISSN:1559-6095
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipids are essential biomolecules with diverse biological functions, ranging from building blocks for all biological membranes to energy substrates, signaling molecules, and protein modifiers. Despite advances in lipid analytics by mass spectrometry, the extraction and quantitative analysis of the diverse classes of lipids are still an experimental challenge. Yeast is a model organism that provides several advantages for studying lipid metabolism, because most biosynthetic pathways are well described and a great deal of information is available on the regulatory mechanisms that control lipid homeostasis. In addition, the composition of yeast lipids is much less complex than that of mammalian lipids, making yeast an excellent reference system for studying lipid-associated cell functions.
[Mh] Termos MeSH primário: Lipídeos/análise
Leveduras/química
[Mh] Termos MeSH secundário: Ácidos Graxos/análise
Glicerofosfolipídeos/análise
Homeostase
Metabolismo dos Lipídeos
Lipídeos/química
Lipídeos/fisiologia
Saccharomyces cerevisiae/química
Especificidade da Espécie
Esfingolipídeos/análise
Esteróis/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Glycerophospholipids); 0 (Lipids); 0 (Sphingolipids); 0 (Sterols)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1101/pdb.top078956


  7 / 7499 MEDLINE  
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[PMID]:28461654
[Au] Autor:Knittelfelder OL; Kohlwein SD
[Ad] Endereço:Institute of Molecular Biosciences, University of Graz, BioTechMed Graz, 8010 Graz, Austria.
[Ti] Título:Quantitative Analysis of Yeast Phospholipids and Sterols by High-Performance Liquid Chromatography-Evaporative Light-Scattering Detection.
[So] Source:Cold Spring Harb Protoc;2017(5):pdb.prot085472, 2017 May 01.
[Is] ISSN:1559-6095
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Normal-phase high-performance liquid chromatography (HPLC) is a standard method for separating the major lipid classes in an extract. Owing to the absence of a common property like light absorbance in the various lipid classes, evaporative light-scattering detection (ELSD) is the method of choice for qualitative and quantitative lipid detection. In most cases, neutral lipids and polar lipids are separated by different solvent systems, making it necessary to perform multiple analyses. Compared with other techniques like thin-layer chromatography, normal-phase HPLC-ELSD has better reproducibility and allows a higher degree of automation. Here we describe a method for separating and quantifying yeast neutral lipids and glycerophospholipids in one analytical run.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Fosfolipídeos/análise
Esteróis/análise
[Mh] Termos MeSH secundário: Difusão Dinâmica da Luz
Glicerofosfolipídeos/análise
Glicerofosfolipídeos/isolamento & purificação
Indicadores e Reagentes
Luz
Fosfolipídeos/isolamento & purificação
Reprodutibilidade dos Testes
Espalhamento de Radiação
Esteróis/isolamento & purificação
Leveduras
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycerophospholipids); 0 (Indicators and Reagents); 0 (Phospholipids); 0 (Sterols)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1101/pdb.prot085472


  8 / 7499 MEDLINE  
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[PMID]:29236780
[Au] Autor:Wang CC; Sulli M; Fu DQ
[Ad] Endereço:Fruit Biology Laboratory, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
[Ti] Título:The role of phytochromes in regulating biosynthesis of sterol glycoalkaloid in eggplant leaves.
[So] Source:PLoS One;12(12):e0189481, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycoalkaloids are toxic compounds that are synthesized by many Solanum species. Glycoalkaloid biosynthesis is influenced by plant genetic and environmental conditions. Although many studies have shown that light is an important factor affecting glycoalkaloid biosynthesis, the specific mechanism is currently unknown. Chlorophyll and carotenoid biosynthesis depend on light signal transduction and share some intermediate metabolites with the glycoalkaloid biosynthetic pathway. Here, we used virus-induced gene silencing to silence genes encoding phytoene desaturase (PDS) and magnesium chelatase (CHLI and CHLH) to reduce chlorophyll and carotenoid levels in eggplant leaves. Quantification of carotenoid and chlorophyll levels is analyzed by LC/PDA/APCI/MS and semipolar metabolite profiling by LC/HESI/MS. Notably, the resulting lines showed decreases in glycoalkaloid production. We further found that the expression of some genes involved in the production of glycoalkaloids and other metabolites were suppressed in these silenced lines. Our results indicate that photosynthetic pigment accumulation affects steroidal glycoalkaloid biosynthesis in eggplant leaves. This finding lays the foundation for reducing the levels of endogenous antinutritional compounds in crops.
[Mh] Termos MeSH primário: Alcaloides/biossíntese
Oxirredutases/metabolismo
Fitocromo/metabolismo
Folhas de Planta/metabolismo
Solanum melongena/metabolismo
Esteróis/biossíntese
[Mh] Termos MeSH secundário: Cromatografia Líquida
Espectrometria de Massas
Solanum melongena/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Sterols); 11121-56-5 (Phytochrome); EC 1.- (Oxidoreductases); EC 1.14.99.- (phytoene dehydrogenase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189481


  9 / 7499 MEDLINE  
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[PMID]:29173820
[Au] Autor:Encinar Del Dedo J; Idrissi FZ; Fernandez-Golbano IM; Garcia P; Rebollo E; Krzyzanowski MK; Grötsch H; Geli MI
[Ad] Endereço:Institute for Molecular Biology of Barcelona (CSIC), Baldiri Reixac 15, 08028 Barcelona, Spain.
[Ti] Título:ORP-Mediated ER Contact with Endocytic Sites Facilitates Actin Polymerization.
[So] Source:Dev Cell;43(5):588-602.e6, 2017 Dec 04.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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. Disruption of the ER contact with endocytic sites using ORP, VAP, myosin-I, or reticulon mutants delays and weakens actin polymerization and interferes with vesicle scission. Finally, we provide evidence suggesting that ORP-dependent sterol transfer facilitates actin polymerization at endocytic sites.
[Mh] Termos MeSH primário: Actinas/metabolismo
Retículo Endoplasmático/metabolismo
Metabolismo dos Lipídeos/fisiologia
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Miosina Tipo I/metabolismo
Receptores de Esteroides/metabolismo
Saccharomyces cerevisiae/metabolismo
Esteróis/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Receptors, Steroid); 0 (Sterols); 0 (oxysterol binding protein); EC 3.6.1.- (Myosin Type I)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  10 / 7499 MEDLINE  
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[PMID]:28453654
[Au] Autor:Takishita K; Takaki Y; Chikaraishi Y; Ikuta T; Ozawa G; Yoshida T; Ohkouchi N; Fujikura K
[Ad] Endereço:Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Kanagawa, Japan.
[Ti] Título:Genomic Evidence that Methanotrophic Endosymbionts Likely Provide Deep-Sea Bathymodiolus Mussels with a Sterol Intermediate in Cholesterol Biosynthesis.
[So] Source:Genome Biol Evol;9(5):1148-1160, 2017 05 01.
[Is] ISSN:1759-6653
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Sterols are key cyclic triterpenoid lipid components of eukaryotic cellular membranes, which are synthesized through complex multi-enzyme pathways. Similar to most animals, Bathymodiolus mussels, which inhabit deep-sea chemosynthetic ecosystems and harbor methanotrophic and/or thiotrophic bacterial endosymbionts, possess cholesterol as their main sterol. Based on the stable carbon isotope analyses, it has been suggested that host Bathymodiolus mussels synthesize cholesterol using a sterol intermediate derived from the methanotrophic endosymbionts. To test this hypothesis, we sequenced the genome of the methanotrophic endosymbiont in Bathymodiolus platifrons. The genome sequence data demonstrated that the endosymbiont potentially generates up to 4,4-dimethyl-cholesta-8,14,24-trienol, a sterol intermediate in cholesterol biosynthesis, from methane. In addition, transcripts for a subset of the enzymes of the biosynthetic pathway to cholesterol downstream from a sterol intermediate derived from methanotroph endosymbionts were detected in our transcriptome data for B. platifrons. These findings suggest that this mussel can de novo synthesize cholesterol from methane in cooperation with the symbionts. By in situ hybridization analyses, we showed that genes associated with cholesterol biosynthesis from both host and endosymbionts were expressed exclusively in the gill epithelial bacteriocytes containing endosymbionts. Thus, cholesterol production is probably localized within these specialized cells of the gill. Considering that the host mussel cannot de novo synthesize cholesterol and depends largely on endosymbionts for nutrition, the capacity of endosymbionts to synthesize sterols may be important in establishing symbiont-host relationships in these chemosynthetic mussels.
[Mh] Termos MeSH primário: Bactérias/genética
Bactérias/metabolismo
Bivalves/microbiologia
Colesterol/biossíntese
[Mh] Termos MeSH secundário: Animais
Bivalves/química
Bivalves/citologia
Bivalves/metabolismo
Membrana Celular/química
Perfilação da Expressão Gênica
Filogenia
Esteróis/biossíntese
Simbiose
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Sterols); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171206
[Lr] Data última revisão:
171206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/gbe/evx082



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