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amino acid starvation

Nanako Kanno, Katsumi Matsuura, Shin Haruta
Purple photosynthetic bacteria utilize light energy for growth. We previously demonstrated that light energy contributed to prolonging the survival of multiple purple bacteria under carbon-starved conditions. In order to clarify the effects of illumination on metabolic states under carbon-starved, non-growing conditions, we herein compared the metabolic profiles of starved cells in the light and dark using the purple bacterium, Rhodopseudomonas palustris. The metabolic profiles of starved cells in the light were markedly different from those in the dark...
March 13, 2018: Microbes and Environments
Masanori Izumi, Sakuya Nakamura
Most assimilated nutrients in the leaves of land plants are stored in chloroplasts as photosynthetic proteins, where they mediate CO₂ assimilation during growth. During senescence or under suboptimal conditions, chloroplast proteins are degraded, and the amino acids released during this process are used to produce young tissues, seeds, or respiratory energy. Protein degradation machineries contribute to the quality control of chloroplasts by removing damaged proteins caused by excess energy from sunlight...
March 12, 2018: International Journal of Molecular Sciences
Simon R Law, Daria Chrobok, Marta Juvany, Nicolas Delhomme, Pernilla Lindén, Bastiaan Brouwer, Abdul Ahad, Thomas Moritz, Stefan Jansson, Per Gardestrom, Olivier Keech
In plants, an individually darkened leaf (IDL) initiates senescence much more rapidly than a leaf from a whole darkened plant (DP). Combining transcriptomic and metabolomic approaches in Arabidopsis thaliana, we present an overview of the metabolic strategies that are employed in response to different darkening treatments. Under DP conditions, the perception of carbon starvation drove a profound metabolic readjustment in which lipids, branched-chain amino acids, and potentially monosaccharides released from cell wall loosening became important substrates for maintaining minimal ATP production...
March 9, 2018: Plant Physiology
Cynthia L Hsu, Elian X Lee, Kara L Gordon, Edwin A Paz, Wen-Chuan Shen, Kohta Ohnishi, Jill Meisenhelder, Tony Hunter, Albert R La Spada
Autophagy is the major cellular pathway by which macromolecules are degraded, and amino acid depletion powerfully activates autophagy. MAP4K3, or germinal-center kinase-like kinase, is required for robust cell growth in response to amino acids, but the basis for MAP4K3 regulation of cellular metabolic disposition remains unknown. Here we identify MAP4K3 as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy, and through amino acid starvation-dependent lysosomal localization of MAP4K3...
March 5, 2018: Nature Communications
Chinwendu Nwadike, Leon E Williamson, Laura E Gallagher, Jun-Lin Guan, Edmond Y W Chan
Autophagy maintains metabolism in response to starvation but each nutrient is sensed distinctly. Amino acid deficiency suppresses mechanistic target of rapamycin complex 1 (MTORC1) while glucose deficiency promotes AMP-activated protein kinase (AMPK). MTORC1 and AMPK signalling pathways converge onto the ULK1/2 autophagy initiation complex. Here, we show that amino acid starvation promoted formation of ULK1- and Sequestosome1/p62-positive early autophagosomes. Autophagosome initiation was controlled by MTORC1 sensing glutamine, leucine and arginine levels together...
March 5, 2018: Molecular and Cellular Biology
Chaochao Luo, Shengguo Zhao, Muchen Zhang, Yanan Gao, Jiaqi Wang, Mark D Hanigan, Nan Zheng
Amino acids (AA) are one of the key nutrients that regulate cell proliferation and casein synthesis in cow mammary epithelial cells (CMEC), but the mechanism of this regulation is not yet clear. In this study, the effect of SESN2 on AA-mediated cell proliferation and casein synthesis in CMEC was assessed. After 12 h of AA starvation, CMECs were cultured in the absence of all AA (AA-), in the presences of only essential AA (EAA+), or of all AA (AA+). Cell proliferation, casein expression, and activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway were increased; but SESN2 expression was decreased in response to increased EAA or AA supply...
March 2, 2018: Scientific Reports
Ajda Coker Gurkan, Elif Damla Arisan, Pinar Obakan Yerlikaya, Halime Ilhan, Narcin Palavan Unsal
PURPOSE: One of the recently developed polyamine (PA) analogues, N1 ,N11 -diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells...
February 28, 2018: Cellular Oncology (Dordrecht)
Yu Saito, Shota Moriya, Hiromi Kazama, Kazuhiro Hirasawa, Kana Miyahara, Hiroko Kokuba, Hirotsugu Hino, Hiroyuki Kikuchi, Naoharu Takano, Masaki Hiramoto, Kiyoaki Tsukahara, Keisuke Miyazawa
The maintenance of the intracellular level of amino acids is crucial for cellular homeostasis. This is carried out via the regulation of both the influx from the extracellular environment and the recycling of intracellular resources. Since epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, including gefitinib (GEF) have been reported to induce the apoptosis of several cancer cell lines, in the present study, we examined whether the cytotoxic effects of GEF are further enhanced under amino acid starvation (AAS) culture conditions...
February 23, 2018: International Journal of Oncology
Adam Lassak, Mathew Dean, Dorota Wyczechowska, Anna Wilk, Luis Marrero, Jimena Trillo-Tinoco, A Hamid Boulares, Jann N Sarkaria, Luis Del Valle, Francesca Peruzzi, Augusto Ochoa, Krzysztof Reiss
Insulin receptor substrate 1 (IRS-1) is a common cytosolic adaptor molecule involved in signal transduction from insulin and IGF-1 receptors. IRS-1 can also be found in the nucleus. We report here a new finding of unique IRS-1 nuclear structures, which we observed initially in glioblastoma biopsies and glioblastoma xenografts. These nuclear structures can be reproduced in vitro by ectopic expression of IRS-1 cDNA cloned in frame with nuclear localization signal (NLS-IRS-1). In these structures, IRS-1 localizes at the periphery while the center harbors a key autophagy protein, LC3...
February 26, 2018: Molecular and Cellular Biology
Philip H Iffland, Marianna Baybis, Allan E Barnes, Richard J Leventer, Paul J Lockhart, Peter B Crino
Mutations in DEPDC5 and NPRL3 subunits of GATOR1, a modulator of mechanistic target of rapamycin (mTOR), are linked to malformations of cortical development (MCD). Brain specimens from these individuals reveal abnormal cortical lamination, altered cell morphology, and hyperphosphorylation of ribosomal S6 protein (PS6), a marker for mTOR activation. While numerous studies have examined GATOR1 subunit function in non-neuronal cell lines, few have directly assessed loss of GATOR 1 subunit function in neuronal cell types...
February 23, 2018: Neurobiology of Disease
Galina V Smirnova, Aleksey V Tyulenev, Nadezda G Muzyka, Oleg N Oktyabrsky
Amino acid starvation causes an RelA-dependent increase in the regulatory nucleotide (p)ppGpp that leads to pleiotropic changes in Escheria coli metabolism, but the role of (p)ppGpp in regulation of respiration remains unclear. Here we demonstrate that amino acid starvation is accompanied by sharp RelA-dependent inhibition of respiration. The sharp phase of inhibition is absent in relA mutants, and can be prevented by translation inhibitors chloramphenicol and tetracycline, which abolish accumulation of (p)ppGpp...
February 22, 2018: Research in Microbiology
Amanda J Brinkworth, Mark R Wildung, Rey A Carabeo
Iron is essential for growth and development of Chlamydia . Its long-term starvation in cultured mammalian cells leads to production of aberrant noninfectious chlamydial forms, also known as persistence. Immediate transcriptional responses to iron limitation have not been characterized, leaving a knowledge gap of how Chlamydia regulates its response to changes in iron availability. We used the fast-chelating agent 2,2'-bipyridyl (BPDL) to homogeneously starve Chlamydia trachomatis serovar L2 of iron, starting at 6 or 12 h postinfection...
January 2018: MSystems
Caia D S Duncan, María Rodríguez-López, Phil Ruis, Jürg Bähler, Juan Mata
Eukaryotes respond to amino acid starvation by enhancing the translation of mRNAs encoding b-ZIP family transcription factors (GCN4 in Saccharomyces cerevisiae and ATF4 in mammals), which launch transcriptional programs to counter this stress. This pathway involves phosphorylation of the eIF2 translation factor by Gcn2-protein kinases and is regulated by upstream ORFs (uORFs) in the GCN4/ATF4 5' leaders. Here, we present evidence that the transcription factors that mediate this response are not evolutionarily conserved...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jun Zhou, Ji Wan, Xin Erica Shu, Yuanhui Mao, Xiao-Min Liu, Xin Yuan, Xingqian Zhang, Martin E Hess, Jens C Brüning, Shu-Bing Qian
The integrated stress response (ISR) facilitates cellular adaptation to stress conditions via the common target eIF2α. During ISR, the selective translation of stress-related mRNAs often relies on alternative mechanisms, such as leaky scanning or reinitiation, but the underlying mechanism remains incompletely understood. Here we report that, in response to amino acid starvation, the reinitiation of ATF4 is not only governed by the eIF2α signaling pathway, but is also subjected to regulation by mRNA methylation in the form of N6-methyladenosine (m6A)...
February 1, 2018: Molecular Cell
Qiuwen He, Chenxia Cao, Wenyan Hui, Jie Yu, Heping Zhang, Wenyi Zhang
Lactobacillus plantarum, commonly isolated from plant material, is widely used to produce various types of fermented foods. However, nutrient-limiting conditions are often encountered during industrial applications. The present study aimed to investigate the response of L. plantarum P-8 to glucose-limited conditions in a long-term experiment. Genotypic and proteomic changes in L. plantarum P-8 were monitored over 3 years in glucose-limited and glucose-normal media using whole-genome resequencing and tandem mass tag-based quantitative proteomic analysis...
January 29, 2018: Journal of Proteomics
Hyang-Gi Ji, Yeong-Ran Lee, Min-Seuk Lee, Kyeong-Hwan Hwang, Clara Yongjoo Park, Eun-Hee Kim, Jun Seong Park, Young-Shick Hong
With increase of tea (Camellia sinensis) consumption, its chemical or metabolite compositions play a crucial role in the determination of tea quality. In general, metabolite compositions of fresh tea leaves including shoots depend on plucking seasons and tea cultivators. Therefore, choosing specific plucking time of tea leaves can provide use-specified tea products. Artificial control of tea growing, typically shade treatments, can lead to significant changes of the tea metabolite compositions of tea. However, metabolic characteristics of tea grown under various shade treatments conditions remain unclear...
February 6, 2018: Journal of Agricultural and Food Chemistry
Jie Yu, Wenyan Hui, ChenXia Cao, Lin Pan, Heping Zhang, Wenyi Zhang
Nutrient starvation is an important survival challenge for bacteria during industrial production of functional foods. As next-generation sequencing technology has greatly advanced, we performed proteomic and genomic analysis to investigate the response of Lactobacillus casei Zhang to a glucose-restricted environment. L. casei Zhang strains were permitted to evolve in glucose-restricted or normal medium from a common ancestor over a 3-year period, and they were sampled at 1000, 2000, 3000, 4000, 5000, 6000, 7000, and 8000 generations and subjected to proteomic and genomic analyses...
February 6, 2018: Journal of Proteome Research
Mark Thomas, Tanja Davis, Ben Loos, Balindiwe Sishi, Barbara Huisamen, Hans Strijdom, Anna-Mart Engelbrecht
Autophagy plays a major role in the adaptive metabolic response of cancer cells during adverse conditions such as nutrient deprivation. However, specific data that assess metabolite profiles in context with adenosine triphosphate (ATP) availability and cell death susceptibility remain limited. Human breast cancer cells, MDAMB231, and normal breast epithelial cells, MCF12A, were subjected to short-term amino acid starvation and the cellular apoptotic and autophagic responses assessed. The role of autophagy in the control of cellular amino acid, ATP, free fatty acid, and glucose levels during amino acid starvation were compared...
February 5, 2018: Cell Biochemistry and Function
Takaaki Hirota, Masanori Izumi, Shinya Wada, Amane Makino, Hiroyuki Ishida
The vacuolar lytic degradation of proteins releases free amino acids (AAs) that plants can use instead of sugars for respiratory energy production. Autophagy is a major cellular process leading to the transport of proteins into the vacuole for degradation. Here, we examine the contribution of autophagy to the AA metabolism response to sugar starvation in mature leaves of Arabidopsis thaliana. During sugar starvation arising from the exposure of wild-type (WT) plants to darkness, autophagic transport of chloroplast stroma, which contains most of the proteins in a leaf, into the vacuolar lumen was induced within two days...
January 30, 2018: Plant & Cell Physiology
Pavel Kudrin, Ievgen Dzhygyr, Kensuke Ishiguro, Jelena Beljantseva, Elena Maksimova, Sofia Raquel Alves Oliveira, Vallo Varik, Roshani Payoe, Andrey L Konevega, Tanel Tenson, Tsutomu Suzuki, Vasili Hauryliuk
During amino acid starvation the Escherichia coli stringent response factor RelA recognizes deacylated tRNA in the ribosomal A-site. This interaction activates RelA-mediated synthesis of alarmone nucleotides pppGpp and ppGpp, collectively referred to as (p)ppGpp. These two alarmones are synthesized by addition of a pyrophosphate moiety to the 3' position of the abundant cellular nucleotide GTP and less abundant nucleotide GDP, respectively. Using untagged native RelA we show that allosteric activation of RelA by pppGpp increases the efficiency of GDP conversion to achieve the maximum rate of (p)ppGpp production...
January 30, 2018: Nucleic Acids Research
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