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https://www.readbyqxmd.com/read/29455333/stress-response-factors-drive-regrowth-of-quiescent-cells
#1
REVIEW
Zheng Kuang, Hongkai Ji, Jef D Boeke
Quiescent cells exploit an array of transcription factors to activate stress response machinery and maintain survival under nutrient-limited conditions. Our recent findings reveal that these transcription factors also play an important role in the exit of quiescence and regrowth. By studying Saccharomyces cerevisiae under a continuous, nutrient-limited condition, we found that Msn2 and Msn4 function as master regulators of glycolytic genes in the quiescent-like phase. They control the timing of transition from quiescence to growth by regulating the accumulation rate of acetyl-CoA, a key metabolite that is downstream of glycolysis and drives growth...
February 17, 2018: Current Genetics
https://www.readbyqxmd.com/read/29454998/a-cell-death-assay-for-assessing-the-mitochondrial-targeting-of-proteins
#2
Daniel Camara Teixeira, Elizabeth L Cordonier, Subhashinee S K Wijeratne, Patricia Huebbe, Augusta Jamin, Sarah Jarecke, Matthew Wiebe, Janos Zempleni
The mitochondrial proteome comprises 1000 to 1500 proteins, in addition to proteins for which the mitochondrial localization is uncertain. About 800 diseases have been linked with mutations in mitochondrial proteins. We devised a cell survival assay for assessing the mitochondrial localization in a high-throughput format. This protocol allows us to assess the mitochondrial localization of proteins and their mutants, and to identify drugs and nutrients that modulate the mitochondrial targeting of proteins. The assay works equally well for proteins directed to the outer mitochondrial membrane, inner mitochondrial membrane mitochondrial and mitochondrial matrix, as demonstrated by assessing the mitochondrial targeting of the following proteins: carnitine palmitoyl transferase 1 (consensus sequence and R123C mutant), acetyl-CoA carboxylase 2, uncoupling protein 1 and holocarboxylase synthetase...
January 31, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29453986/sterol-o-acyltransferase-1-deficiency-improves-defective-insulin-signaling-in-the-brains-of-mice-fed-a-high-fat-diet
#3
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453276/entropy-drives-selective-fluorine-recognition-in-the-fluoroacetyl-coa-thioesterase-from-streptomyces-cattleya
#4
Amy M Weeks, Ningkun Wang, Jeffrey G Pelton, Michelle C Y Chang
Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. As such, there is strong interest in developing a deeper understanding of how fluorine affects the interaction of these ligands with their targets. Given the small number of fluorinated metabolites identified to date, insights into fluorine recognition have been provided almost entirely by synthetic systems. The fluoroacetyl-CoA thioesterase (FlK) from Streptomyces cattleya thus provides a unique opportunity to study an enzyme-ligand pair that has been evolutionarily optimized for a surprisingly high 10 6 selectivity for a single fluorine substituent...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29449592/first-evidence-for-a-multienzyme-complex-of-lipid-biosynthesis-pathway-enzymes-in-cunninghamella-bainieri
#5
Shuwahida Shuib, Izyanti Ibrahim, Mukram Mohamed Mackeen, Colin Ratledge, Aidil Abdul Hamid
Malic enzyme (ME) plays a vital role in determining the extent of lipid accumulation in oleaginous fungi being the major provider of NADPH for the activity of fatty acid synthase (FAS). We report here the first direct evidence of the existence of a lipogenic multienzyme complex (the lipid metabolon) involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and lipid accumulation phases were prepared by protoplasting and subjected to Blue Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#6
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29441719/azd1208-a-pan-pim-kinase-inhibitor-inhibits-adipogenesis-and-induces-lipolysis-in-3t3-l1-adipocytes
#7
Yu-Kyoung Park, Brice Wilfried Obiang-Obounou, Kyung-Bok Lee, Jong-Soon Choi, Byeong-Churl Jang
The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD1208 is a pan-Pim kinase inhibitor and is known for its anti-cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3-L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3-L1 cells, suggesting the drug's anti-adipogenic effect...
February 14, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29438065/cytosolic-carnitine-acetyltransferase-as-a-source-of-cytosolic-acetyl-coa-a-possible-mechanism-for-regulation-of-cardiac-energy-metabolism
#8
Tariq R Altamimi, Panakkezhum D Thomas, Ahmed M Darwesh, Natasha Fillmore, Mohammad U Mahmoud, Liyan Zhang, Abhishek Gupta, Rami Al Batran, John M Seubert, Gary Lopaschuk
The role of carnitine acetyltransferase (CrAT) in regulating cardiac energy metabolism is poorly understood. CrAT modulates mitochondrial acetyl-CoA/CoA ratios, thus regulating pyruvate dehydrogenase activity and glucose oxidation. Here we propose that cardiac CrAT also provides cytosolic acetyl-CoA for the production of malonyl-CoA, a potent inhibitor of fatty acid oxidation. We show that murine heart cytosol has higher reverse CrAT activity (RCrAT, producing acetyl-CoA from acetylcarnitine) compared to liver, which primarily uses ATP-citrate lyase to produce cytosolic acetyl-CoA for lipogenesis...
February 7, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29435719/adaptation-of-the-secretome-of-echinostoma-caproni-may-contribute-to-parasite-survival-in-a-th1-milieu
#9
Alba Cortés, Carla Muñoz-Antolí, María Álvarez-Izquierdo, Javier Sotillo, J Guillermo Esteban, Rafael Toledo
Echinostoma caproni (Trematoda: Echinostomatidae) is an intestinal trematode, broadly employed to study the host-dependent mechanisms that govern the evolution of intestinal helminth infections. Resistance against E. caproni homologous secondary infections has been reported in mice and appears to be related to the generation of a local Th2 response, whereas Th1 responses promote the development of chronic primary infections. Herein, the ability of E. caproni to modulate its secretome according to the host environment is investigated...
February 12, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29433631/ampk-signaling-to-acetyl-coa-carboxylase-is-required-for-fasting-and-cold-induced-appetite-but-not-thermogenesis
#10
Sandra Galic, Kim Loh, Lisa Murray-Segal, Gregory R Steinberg, Zane B Andrews, Bruce E Kemp
AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. AMPK inhibits fatty acid synthesis and promotes fatty acid oxidation by phosphorylation of acetyl-CoA carboxylase (ACC) 1 at Ser 79 and ACC2 at Ser 212 . Using mice with Ser 79 Ala/Ser 212 Ala knock-in mutations (ACC DKI) we find that inhibition of ACC phosphorylation leads to reduced appetite in response to fasting or cold exposure. At sub-thermoneutral temperatures, ACC DKI mice maintain normal energy expenditure and thermogenesis, but fail to increase appetite and lose weight...
February 13, 2018: ELife
https://www.readbyqxmd.com/read/29432553/short-term-heat-stress-altered-metabolism-and-insulin-signaling-in-skeletal-muscle
#11
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29432413/comprehensive-analysis-of-central-carbon-metabolism-illuminates-connections-between-nutrient-availability-growth-rate-and-cell-morphology-in-escherichia-coli
#12
Corey S Westfall, Petra Anne Levin
Bacterial morphology is a complex trait that is highly sensitive to changes in the environment. For heterotrophic organisms, such as Escherichia coli, increases in nutrient levels are frequently accompanied by several-fold increases in both size and growth rate. Despite the dramatic nature of these changes, how alterations in nutrient availability translate into changes in growth and morphology remains a largely open question. To understand the signaling networks coupling nutrient availability with size and shape, we examined the impact of deletions in the entirety of non-essential central carbon metabolic genes on E...
February 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29429925/a-metabolic-basis-for-endothelial-to-mesenchymal-transition
#13
Jianhua Xiong, Hiroyuki Kawagishi, Ye Yan, Jie Liu, Quinn S Wells, Lia R Edmunds, Maria M Fergusson, Zu-Xi Yu, Ilsa I Rovira, Evan L Brittain, Michael J Wolfgang, Michael J Jurczak, Joshua P Fessel, Toren Finkel
Endothelial-to-mesenchymal transition (EndoMT) is a cellular process often initiated by the transforming growth factor β (TGF-β) family of ligands. Although required for normal heart valve development, deregulated EndoMT is linked to a wide range of pathological conditions. Here, we demonstrate that endothelial fatty acid oxidation (FAO) is a critical in vitro and in vivo regulator of EndoMT. We further show that this FAO-dependent metabolic regulation of EndoMT occurs through alterations in intracellular acetyl-CoA levels...
February 7, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29423831/targeted-versus-untargeted-omics-the-cafsa-story
#14
Maria Del Mar Amador, Benoit Colsch, Foudil Lamari, Claude Jardel, Farid Ichou, Agnès Rastetter, Frédéric Sedel, Fabien Jourdan, Clément Frainay, Ronald A Wevers, Emmanuel Roze, Christel Depienne, Christophe Junot, Fanny Mochel
BACKGROUND: In 2009, untargeted metabolomics led to the delineation of a new clinico-biological entity called cerebellar ataxia with elevated cerebrospinal free sialic acid, or CAFSA. In order to elucidate CAFSA, we applied sequentially targeted and untargeted omic approaches. METHODS AND RESULTS: First, we studied five of the six CAFSA patients initially described. Besides increased CSF free sialic acid concentrations, three patients presented with markedly decreased 5-methyltetrahydrofolate (5-MTHF) CSF concentrations...
February 8, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29423634/critical-steps-in-carbon-metabolism-affecting-lipid-accumulation-and-their-regulation-in-oleaginous-microorganisms
#15
REVIEW
Marianna Dourou, Dimitra Aggeli, Seraphim Papanikolaou, George Aggelis
Oleaginous microorganisms are able to convert numerous agro-industrial and municipal wastes into storage lipids (single cell oil (SCO)) and are therefore considered as potential biofuel producers. While from an environmental and technological point of view the idea to convert waste materials into fuels is very attractive, the production cost of SCO is not currently competitive to that of conventional oils due to the low productivity of oleaginous microorganisms in combination with the high fermentation cost...
February 8, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29422886/screening-phosphorylation-site-mutations-in-yeast-acetyl-coa-carboxylase-using-malonyl-coa-sensor-to-improve-malonyl-coa-derived-product
#16
Xiaoxu Chen, Xiaoyu Yang, Yu Shen, Jin Hou, Xiaoming Bao
Malonyl-coenzyme A (malonyl-CoA) is a critical precursor for the biosynthesis of a variety of biochemicals. It is synthesized by the catalysis of acetyl-CoA carboxylase (Acc1p), which was demonstrated to be deactivated by the phosphorylation of Snf1 protein kinase in yeast. In this study, we designed a synthetic malonyl-CoA biosensor and used it to screen phosphorylation site mutations of Acc1p in Saccharomyces cerevisiae. Thirteen phosphorylation sites were mutated, and a combination of three site mutations in Acc1p, S686A, S659A, and S1157A, was found to increase malonyl-CoA availability...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29420726/identification-and-validation-of-appropriate-reference-genes-for-qrt-pcr-analysis-in-corynebacterium-glutamicum
#17
XinYue Wang, Feng Peng, Guibin Dong, Yang Sun, Xiaofeng Dai, Yankun Yang, Xiuxia Liu, Zhonghu Bai
Real-time quantitative PCR (qRT-PCR) is a fast and efficient technology for detecting gene expression levels in the study of the Corynebacterium glutamicum protein expression system, but it requires normalization to ensure the reliability of the results obtained. We selected 13 genes from the commonly used housekeeping genes and from transcriptome data as candidate reference genes. The Ct values of the 13 genes were obtained by qRT-PCR at different fermentation stages and under three stress conditions (temperature, acid, and salt)...
February 6, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/29416012/ros-independent-er-stress-mediated-nrf2-activation-promotes-warburg-effect-to-maintain-stemness-associated-properties-of-cancer-initiating-cells
#18
Ching-Wen Chang, Yu-Syuan Chen, Yeou-Guang Tsay, Chia-Li Han, Yu-Ju Chen, Cheng-Chieh Yang, Kai-Feng Hung, Chao-Hsiung Lin, Tsung-Yen Huang, Shou-Yen Kao, Te-Chang Lee, Jeng-Fan Lo
Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROSLow cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings. Herein, we first showed CICs mainly relying on glycolysis that was important for the maintenance of stemness properties...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29410419/methane-utilization-in-methylomicrobium-alcaliphilum-20zr-a-systems-approach
#19
Ilya R Akberdin, Merlin Thompson, Richard Hamilton, Nalini Desai, Danny Alexander, Calvin A Henard, Michael T Guarnieri, Marina G Kalyuzhnaya
Biological methane utilization, one of the main sinks of the greenhouse gas in nature, represents an attractive platform for production of fuels and value-added chemicals. Despite the progress made in our understanding of the individual parts of methane utilization, our knowledge of how the whole-cell metabolic network is organized and coordinated is limited. Attractive growth and methane-conversion rates, a complete and expert-annotated genome sequence, as well as large enzymatic, 13C-labeling, and transcriptomic datasets make Methylomicrobium alcaliphilum 20ZR an exceptional model system for investigating methane utilization networks...
February 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29409330/bifidobacteria-and-its-rice-fermented-products-on-diet-induced-obese-mice-analysis-of-physical-status-serum-profile-and-gene-expressions
#20
M Ray, P K Hor, D Ojha, J P Soren, S N Singh, K C Mondal
Obesity is highly correlated with the dysbiosis of intestinal microbiota, and bifidobacteria are one of the soft targets of this metabolic syndrome. The aim of this study is to evaluate the efficacy of Bifidobacterium sp. MKK4 and rice-based fermented foods on physical, haematological, gut microbiota and lypogenic-lypolytic marker genes in diet-induced obese mice. Adult male mice (21±0.7 g) were randomly divided into four groups (n=10) according to the type of diet: normal diet (ND), high fat diet (HFD), HFD supplemented with Bifidobacterium sp...
February 7, 2018: Beneficial Microbes
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