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Iron sensing metabolic pathway

Peter Hortschansky, Hubertus Haas, Eva M Huber, Michael Groll, Axel A Brakhage
The CCAAT binding complex (CBC), consisting of a heterotrimeric core structure, is highly conserved in eukaryotes and constitutes an important general transcriptional regulator. Scope of the review. In this review we discuss the scientific history and the current state of knowledge of the multiple gene regulatory functions, protein motifs and structure of the CBC in fungi with a special focus on Aspergillus species. Major conclusions and general significance. Initially identified as a transcriptional activator of respiration in Saccharomyces cerevisiae, in other fungal species the CBC was found to be involved in highly diverse pathways, but a general rationale for its involvement was missing...
December 8, 2016: Biochimica et Biophysica Acta
Massimiliano Magro, Luca Fasolato, Emanuela Bonaiuto, Nadia Andrea Andreani, Davide Baratella, Vittorino Corraducci, Giovanni Miotto, Barbara Cardazzo, Fabio Vianello
BACKGROUND: Mineral iron(III) recognition by bacteria is considered a matter of debate. The peculiar surface chemistry of novel naked magnetic nanoparticles, called SAMNs (surface active maghemite nanoparticles) characterized by solvent exposed Fe(3+) sites on their surface, was exploited for studying mineral iron sensing in Pseudomonas fluorescens. METHODS: SAMNs were applied for mimicking Fe(3+) ions in solution, acting as magnetically drivable probes to evaluate putative Fe(3+) recognition sites on the microorganism surface...
October 2016: Biochimica et Biophysica Acta
Miguel C Lucena, Patricia Carvalho-Cruz, Joana L Donadio, Isadora A Oliveira, Rafaela M de Queiroz, Monica M Marinho-Carvalho, Mauro Sola-Penna, Iron F de Paula, Katia C Gondim, Mark E McComb, Catherine E Costello, Stephen A Whelan, Adriane R Todeschini, Wagner B Dias
Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2-5% of the total glucose, generating UDP-GlcNAc as the end product...
June 17, 2016: Journal of Biological Chemistry
Julia Yue Cui, Curtis D Klaassen
The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known xenobiotic-sensing nuclear receptors with overlapping functions. However, there lacks a quantitative characterization to distinguish between the PXR and CAR target genes and signaling pathways in the liver. The present study performed a transcriptomic comparison of the PXR- and CAR-targets using RNA-Seq in livers of adult wild-type mice that were treated with the prototypical PXR ligand PCN (200mg/kg, i.p. once daily for 4days in corn oil) or the prototypical CAR ligand TCPOBOP (3mg/kg, i...
September 2016: Biochimica et Biophysica Acta
W A Weigel, D R Demuth
The QseBC two-component system (TCS) is associated with quorum sensing and functions as a global regulator of virulence. Based on sequence similarity within the sensor domain and conservation of an acidic motif essential for signal recognition, QseBC is primarily distributed in the Enterobacteriaceae and Pasteurellaceae. In Escherichia coli, QseC responds to autoinducer-3 and/or epinephrine/norepinephrine. Binding of epinephrine/norepinephrine is inhibited by adrenergic antagonists; hence QseC functions as a bacterial adrenergic receptor...
October 2016: Molecular Oral Microbiology
Marian Valko, Klaudia Jomova, Christopher J Rhodes, Kamil Kuča, Kamil Musílek
Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive oxygen species, ROS (via the Fenton reaction, which produces hydroxyl radicals), and reactive nitrogen species, RNS, which may cause oxidative damage to biological macromolecules such as DNA, proteins and lipids...
January 2016: Archives of Toxicology
Henriette Irmer, Sonia Tarazona, Christoph Sasse, Patrick Olbermann, Jürgen Loeffler, Sven Krappmann, Ana Conesa, Gerhard H Braus
BACKGROUND: Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long. RESULTS: We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt...
2015: BMC Genomics
Gianpiero Vigani, Franco Faoro, Anna Maria Ferretti, Francesca Cantele, Dario Maffi, Marcello Marelli, Mauro Maver, Irene Murgia, Graziano Zocchi
BACKGROUND: Mitochondria, as recently suggested, might be involved in iron sensing and signalling pathways in plant cells. For a better understanding of the role of these organelles in mediating the Fe deficiency responses in plant cells, it is crucial to provide a full overview of their modifications occurring under Fe-limited conditions. The aim of this work is to characterize the ultrastructural as well as the biochemical changes occurring in leaf mitochondria of cucumber (Cucumis sativus L...
2015: PloS One
John H Hammond, Emily F Dolben, T Jarrod Smith, Sabin Bhuju, Deborah A Hogan
UNLABELLED: In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215...
September 2015: Journal of Bacteriology
Henrique Machado, Eva C Sonnenschein, Jette Melchiorsen, Lone Gram
BACKGROUND: Antibiotic resistance in bacteria spreads quickly, overtaking the pace at which new compounds are discovered and this emphasizes the immediate need to discover new compounds for control of infectious diseases. Terrestrial bacteria have for decades been investigated as a source of bioactive compounds leading to successful applications in pharmaceutical and biotech industries. Marine bacteria have so far not been exploited to the same extent; however, they are believed to harbor a multitude of novel bioactive chemistry...
2015: BMC Genomics
Henrique Machado, Eva C Sonnenschein, Jette Melchiorsen, Lone Gram
BACKGROUND: Antibiotic resistance in bacteria spreads quickly, overtaking the pace at which new compounds are discovered and this emphasizes the immediate need to discover new compounds for control of infectious diseases. Terrestrial bacteria have for decades been investigated as a source of bioactive compounds leading to successful applications in pharmaceutical and biotech industries. Marine bacteria have so far not been exploited to the same extent; however, they are believed to harbor a multitude of novel bioactive chemistry...
2015: BMC Genomics
Robert J Simpson, Andrew T McKie
Iron and oxygen metabolism are intimately linked with one another. A change in the level of either metabolite results in activation of common pathways. At the heart of these responses lies a group of iron and oxygen dependent enzymes called prolyl hydroxylases. Prolyl hydroxylases (PHDs) require both iron and oxygen for optimal activity and their biological activity is to carry out the critical post-translational modification of the addition of a hydroxyl group to specific proline residues within Hypoxia Inducible Factor (HIFs)-well known transcription factors originally thought to regulate responses to hypoxia but which are now known to regulate key iron metabolism proteins too...
February 2015: Metallomics: Integrated Biometal Science
Jérémy Couturier, Jonathan Przybyla-Toscano, Thomas Roret, Claude Didierjean, Nicolas Rouhier
Glutaredoxins (Grxs) are major oxidoreductases involved in the reduction of glutathionylated proteins. Owing to the capacity of several class I Grxs and likely all class II Grxs to incorporate iron-sulfur (Fe-S) clusters, they are also linked to iron metabolism. Most Grxs bind [2Fe-2S] clusters which are oxidatively- and reductively-labile and have identical ligation, involving notably external glutathione. However, subtle differences in the structural organization explain that class II Fe-S Grxs, having more labile and solvent-exposed clusters, can accept Fe-S clusters and transfer them to client proteins, whereas class I Fe-S Grxs usually do not...
June 2015: Biochimica et Biophysica Acta
Jason C Crack, Jeffrey Green, Andrew J Thomson, Nick E Le Brun
Iron-sulfur cluster proteins exhibit a range of physicochemical properties that underpin their functional diversity in biology, which includes roles in electron transfer, catalysis, and gene regulation. Transcriptional regulators that utilize iron-sulfur clusters are a growing group that exploit the redox and coordination properties of the clusters to act as sensors of environmental conditions including O2, oxidative and nitrosative stress, and metabolic nutritional status. To understand the mechanism by which a cluster detects such analytes and then generates modulation of DNA-binding affinity, we have undertaken a combined strategy of in vivo and in vitro studies of a range of regulators...
October 21, 2014: Accounts of Chemical Research
Nunziata Maio, Tracey A Rouault
Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i.e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome...
June 2015: Biochimica et Biophysica Acta
Matthias Kretschmer, Ethan Reiner, Guanggan Hu, Nicola Tam, Debora L Oliveira, Melissa Caza, Ju Hun Yeon, Jeongmi Kim, Christian J Kastrup, Won Hee Jung, James W Kronstad
Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen Cryptococcus neoformans, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. Deletion of the high-affinity uptake system interfered with growth on low-phosphate medium, perturbed the formation of virulence factors (capsule and melanin), reduced survival in macrophages, and attenuated virulence in a mouse model of cryptococcosis...
July 2014: Infection and Immunity
Robert A Quinn, Yan Wei Lim, Heather Maughan, Douglas Conrad, Forest Rohwer, Katrine L Whiteson
The cystic fibrosis (CF) lung contains thick mucus colonized by opportunistic pathogens which adapt to the CF lung environment over decades. The difficulty associated with sampling airways has impeded a thorough examination of the biochemical microhabitats these pathogens are exposed to. An indirect approach is to study the responses of microbial communities to these microhabitats, facilitated by high-throughput sequencing of microbial DNA and RNA from sputum samples. Microbial metagenomes and metatranscriptomes were sequenced from multiple CF patients, and the reads were assigned taxonomy and function through sequence homology to NCBI and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database hierarchies...
2014: MBio
Andrew M Stern, Jun Zhu
Nitric oxide (NO) is a radical gas that has been intensively studied for its role as a bacteriostatic agent. NO reacts in complex ways with biological molecules, especially metal centers and other radicals, to generate other bioactive compounds that inhibit enzymes, oxidize macromolecules, and arrest bacterial growth. Bacteria encounter not only NO derived from the host during infection but also NO derived from other bacteria and inorganic sources. The transcriptional responses used by bacteria to respond to NO are diverse but usually involve an iron-containing transcription factor that binds NO and alters its affinity for either DNA or factors involved in transcription, leading to the production of enzymatic tolerance systems...
2014: Advances in Applied Microbiology
Wen-Shyong Tzou, Ying Chu, Tzung-Yi Lin, Chin-Hwa Hu, Tun-Wen Pai, Hsin-Fu Liu, Han-Jia Lin, Ildeofonso Cases, Ana Rojas, Mayka Sanchez, Zong-Ye You, Ming-Wei Hsu
Adaptation of enzymes in a metabolic pathway can occur not only through changes in amino acid sequences but also through variations in transcriptional activation, mRNA splicing and mRNA translation. The heme biosynthesis pathway, a linear pathway comprised of eight consecutive enzymes in animals, provides researchers with ample information for multiple types of evolutionary analyses performed with respect to the position of each enzyme in the pathway. Through bioinformatics analysis, we found that the protein-coding sequences of all enzymes in this pathway are under strong purifying selection, from cnidarians to mammals...
2014: PloS One
Cornelius Y Taabazuing, John A Hangasky, Michael J Knapp
The ability to sense and adapt to changes in pO2 is crucial for basic metabolism in most organisms, leading to elaborate pathways for sensing hypoxia (low pO2). This review focuses on the mechanisms utilized by mammals and bacteria to sense hypoxia. While responses to acute hypoxia in mammalian tissues lead to altered vascular tension, the molecular mechanism of signal transduction is not well understood. In contrast, chronic hypoxia evokes cellular responses that lead to transcriptional changes mediated by the hypoxia inducible factor (HIF), which is directly controlled by post-translational hydroxylation of HIF by the non-heme Fe(II)/αKG-dependent enzymes FIH and PHD2...
April 2014: Journal of Inorganic Biochemistry
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