amino acid starvation

Yunjun Pan, Liwei Gao, Xiujun Zhang, Yuqi Qin, Guodong Liu, Yinbo Qu
CpcA is a conserved transcriptional activator for the cross-pathway control of amino acid biosynthetic genes in filamentous fungi. Previous studies of this regulator mainly revealed its function under amino acid starvation condition, where amino acid biosynthetic inhibitors were added in the culture. In this study, the biological function of CpcA in Penicillium oxalicum was investigated under different cultivation conditions. Disruption of cpcA led to decreased cell growth either in the presence or absence of histidine biosynthetic inhibitor, and the phenotype could be rescued by the addition of exogenous amino acid sources...
November 7, 2019: Current Microbiology
Rachel Curnock, Alessia Calcagni, Andrea Ballabio, Peter J Cullen
Endosomal recycling maintains the cell surface abundance of nutrient transporters for nutrient uptake, but how the cell integrates nutrient availability with recycling is less well understood. Here, in studying the recycling of human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we establish that following amino acid restriction, the adaptive delivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling. Upon complete amino acid starvation or selective glutamine depletion, we establish that retromer expression is upregulated by transcription factor EB (TFEB) and other members of the MiTF/TFE family of transcription factors through association with CLEAR elements in the promoters of the retromer genes VPS35 and VPS26A TFEB regulation of retromer expression therefore supports adaptive nutrient acquisition through endosomal recycling...
November 6, 2019: Journal of Cell Biology
Thomas Orasch, Anna-Maria Dietl, Yana Shadkchan, Ulrike Binder, Ingo Bauer, Cornelia Lass-Flörl, Nir Osherov, Hubertus Haas
In contrast to mammalia, fungi are able to synthesize the branched-chain amino acid leucine de novo . Recently, the transcription factor LeuB has been shown to cross-regulate leucine biosynthesis, nitrogen metabolism and iron homeostasis in Aspergillus fumigatus , the most common human mold pathogen. Moreover, the leucine biosynthetic pathway intermediate α-isopropylmalate (α-IPM) has previously been shown to posttranslationally activate LeuB homologs in S. cerevisiae and A. nidulans . Here, we demonstrate that in A...
December 2019: Virulence
Thomas Seidel, Dominik J Fiegle, Tim J Baur, Anne Ritzer, Sandra Nay, Christian Heim, Michael Weyand, Hendrik Milting, Robert H Oakley, John A Cidlowski, Tilmann Volk
A major contributor to contractile dysfunction in heart failure is remodelling and loss of the cardiomyocyte transverse tubular system (t-system), but underlying mechanisms and signalling pathways remain elusive. It has been shown that dexamethasone promotes t-tubule development in stem cell-derived cardiomyocytes and that cardiomyocyte-specific glucocorticoid receptor (GR) knockout (GRKO) leads to heart failure. Here, we studied if the t-system is altered in GRKO hearts and if GR signalling is required for t-system preservation in adult cardiomyocytes...
October 31, 2019: Basic Research in Cardiology
Naoko Toshima, Melisa Kantar Weigelt, Aliće Weiglein, Fabian A Boetzl, Bertram Gerber
Amino acids are important nutrients for animals because they are necessary for protein synthesis in particular during growth, as well as for neurotransmission. However, little is known about how animals use past experience to guide their search for amino-acid-rich food. We reasoned that the larvae of Drosophila melanogaster are suitable for investigating this topic because they are the feeding and growth stages in the life cycle of these holometabolous insects. Specifically, we investigated whether experiencing an odour with a 20-amino-acid mixture as a semi-natural tastant during training establishes odour-tastant associative memories...
October 31, 2019: Journal of Experimental Biology
Lina Wu, Miaomiao Zhang, Yiyi Song, Minfang Deng, Shengbing He, Liuqin Su, Yu Chen, Thomas Keith Wood, Xiaomei Yan
Bacterial toxin-antitoxin (TA) systems, which are diverse and widespread among prokaryotes, are responsible for tolerance to drugs and environmental stresses. However, the low abundance of toxin and antitoxin proteins renders their quantitative measurement in single bacteria challenging. Employing a laboratory-built nano-flow cytometer (nFCM) to monitor a tetracysteine (TC)-tagged TA system labelled with the biarsenical dye (FlAsH), we here report the development of a sensitive method that enables the detection of basal-level expression of antitoxin...
October 31, 2019: ACS Chemical Biology
Zhuo Ma, Kayla King, Maha Alqahtani, Madeline Worden, Parthasarathy Muthuraman, Christopher L Cioffi, Chandra Shekhar Bakshi, Meenakshi Malik
Francisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and, based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones...
2019: PloS One
Glenn R Masson
Cells must be able to sense and adapt to their surroundings to thrive in a dynamic environment. Key to adapting to a low nutrient environment is the Integrated Stress Response (ISR), a short-lived pathway that allows cells to either regain cellular homeostasis or facilitate apoptosis during periods of stress. Central to the ISR is the protein kinase General Control Non-depressible 2 (GCN2), which is responsible for sensing starvation. Upon amino acid deficiency, GCN2 is activated and initiates the ISR by phosphorylating the translation initiation factor eIF2α, stalling protein translation, and activating the transcription factor ATF4, which in turn up-regulates autophagy and biosynthesis pathways...
October 11, 2019: Biochemical Society Transactions
Stefano Maggi, Korotoum Yabre, Alberto Ferrari, Camilla Lazzi, Mitsuoki Kawano, Claudio Rivetti, Claudia Folli
Lpt is a 29 amino acid long type I toxin identified in the plasmid DNA of wild Lactobacillus rhamnosus strains isolated from food. We previously reported that transcription of the encoding gene was upregulated under nutritional starvation conditions mimicking cheese ripening environment. The heterologous expression of the Lpt peptide in E. coli resulted in cell growth inhibition, nucleoid condensation and compromised integrity of the cell membrane. Fusion of the Lpt peptide with the fluorescent protein mCherry allowed to visualize the accumulation of the peptide into the membrane, while mutagenesis experiments showed that either the insertion of a negatively charged amino acid into the hydrophobic α-helix or deletion of the hydrophilic C-terminal region, leads to a non-toxic peptide...
October 23, 2019: Scientific Reports
Yongteng Zhao, Hailiang Xing, Xingyu Li, Shuxiang Geng, Delu Ning, Ting Ma, Xuya Yu
In this study, it was found that fulvic acid (FA) enhanced the contents of astaxanthin and lipids in Haematococcus pluvialis under high light and nitrogen starvation conditions by 2- and 1.2-fold, respectively. Meanwhile, the carbohydrate and chlorophyll contents were decreased by FA induction, whereas the levels of reactive oxygen species (ROS) and glutathione (GSH) as well as the expression of astaxanthin and lipid biosynthetic genes were increased. To further explore the interrelation between FA and the biosynthesis of astaxanthin and lipids, a metabolomics analysis of H...
October 23, 2019: Journal of Agricultural and Food Chemistry
Sophie Reidman, Adiel Cohen, Martin Kupiec, Ronit Weisman
The evolutionarily conserved TOR complex 1 (TORC1) activates cell growth and proliferation in response to nutritional signals. In the fission yeast Schizosaccharomyces pombe , TORC1 is essential for vegetative growth, and its activity is regulated in response to nitrogen quantity and quality. Yet, how TORC1 senses nitrogen is poorly understood. Rapamycin, a specific TOR inhibitor, inhibits growth in S. pombe only under conditions in which the activity of TORC1 is compromised. In a genetic screen for rapamycin-sensitive mutations, we isolated caa1-1 , a loss-of-function mutation of the cytosolic form of aspartate aminotransferase (Caa1)...
October 22, 2019: Journal of Biological Chemistry
Huawei Zou, Rui Hu, Zhisheng Wang, Ali Mujtaba Shah, Shaoyu Zeng, Quanhui Peng, Bai Xue, Lizhi Wang, Xiangfei Zhang, Xueying Wang, Junhua Shi, Fengpeng Li, Lei Zeng
Yak suffers severe starvation and body weight reduction in the cold season and recovers relatively rapid growth in the warm season every year. Herein, we investigated the effects of starvation and refeeding on the growth, feed efficiency, blood biochemistry and rumen microbial community as well as functions of yaks. The results showed that starvation significantly reduced the body weight of yaks. Serum glucose and triglyceride concentrations significantly decreased, and β-hydroxybutyric acid and non-esterified fatty acid levels were significantly increased during the starvation period...
October 15, 2019: Animals: An Open Access Journal From MDPI
Travis B Lear, Karina C Lockwood, Yurong Ouyang, John W Evankovich, Mads B Larsen, Bo Lin, Yuan Liu, Bill B Chen
Nutrient sensing is a critical cellular process controlling metabolism and signaling. mTOR complex 1 (mTORC1) is the primary signaling hub for nutrient sensing and, when activated, stimulates anabolic processes while decreasing autophagic flux. mTORC1 receives nutrient status signals from intracellular amino acid sensors. One of these sensors, Sestrin-2, functions as an intracellular sensor of cytosolic leucine and inhibitor of mTORC1 activity. Genetic studies of Sestrin-2 have confirmed its critical role in regulating mTORC1 activity, especially in the case of leucine starvation...
October 4, 2019: Journal of Biological Chemistry
Chisa Y Okada, Akio Nakamura, Kyoko Ogawa, Kazuhiro Kohama, Takako S Kaneko
This study aimed to investigate for the first time, the profile of Physarum microplasmodial phosphatase (PPH) activity toward the phosphorylated light chain of Physarum myosin II (PLCM) at pH 7.6, the velocity of cytoplasmic streaming, and PPH expression in spherule formation during dark starvation (DS). In this study, we cloned the full-length cDNA of PPH using polymerase chain reaction, based on the N-terminal amino acid sequence of the purified enzyme. The cDNA contained an open reading frame (ORF) of 1245 bp, corresponding to 415 amino acids...
September 27, 2019: Cell Biochemistry and Biophysics
Maryam Ghasemitarei, Maksudbek Yusupov, Jamoliddin Razzokov, Babak Shokri, Annemie Bogaerts
We performed computer simulations to investigate the effect of oxidation on the extracellular cystine (CYC) uptake by the xC- antiporter. The latter is important for killing of cancer cells. Specifically, applying molecular dynamics (MD) simulations we studied the transport of CYC across xCT, i.e., the light subunit of the xC- antiporter, in charge of bidirectional transport of CYC and glutamate. We considered the outward facing (OF) configuration of xCT, and to study the effect of oxidation, we modified the Cys327 residue, located in the vicinity of the extracellular milieu, to cysteic acid (CYO327 )...
September 23, 2019: Archives of Biochemistry and Biophysics
Sathish K R Padi, Neha Singh, Jeremiah J Bearss, Virginie Olive, Jin H Song, Marina Cardó-Vila, Andrew S Kraft, Koichi Okumura
The Pim and AKT serine/threonine protein kinases are implicated as drivers of cancer. Their regulation of tumor growth is closely tied to the ability of these enzymes to mainly stimulate protein synthesis by activating mTORC1 (mammalian target of rapamycin complex 1) signaling, although the exact mechanism is not completely understood. mTORC1 activity is normally suppressed by amino acid starvation through a cascade of multiple regulatory protein complexes, e.g., GATOR1, GATOR2, and KICSTOR, that reduce the activity of Rag GTPases...
September 23, 2019: Proceedings of the National Academy of Sciences of the United States of America
Spencer K Cooke, Jacob Russin, Kristen Moulton, Jeffrey Nadel, Inna Loutaev, Qinhua Gu, Zheng Li, Carolyn Beebe Smith
Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene and consequent absence of its protein product, fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that can suppress translation. The absence of FMRP leads to symptoms of FXS including intellectual disability and has been proposed to lead to abnormalities in synaptic plasticity. Synaptic plasticity, protein synthesis and cellular growth pathways have been studied extensively in hippocampal slices from a mouse model of FXS (Fmr1 KO)...
September 20, 2019: Journal of Neurochemistry
Ankita Alexander, Vijay Kumar Singh, Avinash Mishra, Bhavanath Jha
Arachis hypogea (Peanut) is one of the most important crops, and it is harvested and used for food and oil production. Being a legume crop, the fixation of atmospheric nitrogen is achieved through symbiotic association. Nitrogen deficiency is one of the major constrains for loss of crop productivity. The bacterium Stenotrophomonas maltophilia is known for interactions with plants. In this study, characteristics that promote plant growth were explored for their ability to enhance the growth of peanut plants under N2 deficit condition...
2019: PloS One
Kamlesh Pawar, Megumi Shigematsu, Phillipe Loher, Shozo Honda, Isidore Rigoutsos, Yohei Kirino
Post-transcriptional non-template additions of nucleotides to 3'-ends of RNAs play important roles in the stability and function of RNA molecules. Although tRNA nucleotidyltransferase (CCA-adding enzyme) is known to add CCA trinucleotides to 3'-ends of tRNAs, whether other RNA species can be endogenous substrates of CCA-adding enzyme has not been widely explored yet. Herein, we used YAMAT-seq to identify non-tRNA substrates of CCA-adding enzyme. YAMAT-seq captures RNA species that form secondary structures with 4-nt protruding 3'-ends of the sequence 5'-NCCA-3', which is the hallmark structure of RNAs that are generated by CCA-adding enzyme...
September 12, 2019: RNA Biology
Kathryn Jane Turnbull, Ievgen Dzhygyr, Søren Lindemose, Vasili Hauryliuk, Mohammad Roghanian
Amino acid starvation in Escherichia coli activates the enzymatic activity of the stringent factor RelA, leading to accumulation of the alarmone nucleotide (p)ppGpp. The alarmone acts as an intercellular messenger to regulate transcription, translation and metabolism to mediate bacterial stress adaptation. The enzymatic activity of RelA is subject to multi-layered allosteric control executed both by ligands - such as "starved" ribosomal complexes, deacylated tRNA and pppGpp - and by individual RelA domains...
2019: Frontiers in Microbiology
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