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1.
Proc Natl Acad Sci U S A ; 120(5): e2216734120, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36693097

RESUMO

Light energy absorption and transfer are very important processes in photosynthesis. In green sulfur bacteria light is absorbed primarily by the chlorosomes and its energy is transferred via the Fenna-Matthews-Olson (FMO) proteins to a homodimeric reaction center (RC). Here, we report the cryogenic electron microscopic structure of the intact FMO-RC apparatus from Chlorobaculum tepidum at 2.5 Å resolution. The FMO-RC apparatus presents an asymmetric architecture and contains two FMO trimers that show different interaction patterns with the RC core. Furthermore, the two permanently bound transmembrane subunits PscC, which donate electrons to the special pair, interact only with the two large PscA subunits. This structure fills an important gap in our understanding of the transfer of energy from antenna to the electron transport chain of this RC and the transfer of electrons from reduced sulfur compounds to the special pair.


Assuntos
Chlorobi , Complexo de Proteínas do Centro de Reação Fotossintética , Complexo de Proteínas do Centro de Reação Fotossintética/química , Chlorobi/metabolismo , Microscopia Crioeletrônica , Proteínas de Bactérias/metabolismo , Enxofre/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo
2.
Biomolecules ; 13(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36671528

RESUMO

Sulfur is an important element that is incorporated into many biomolecules in humans. The incorporation and transfer of sulfur into biomolecules is, however, facilitated by a series of different sulfurtransferases. Among these sulfurtransferases is the human mercaptopyruvate sulfurtransferase (MPST) also designated as tRNA thiouridine modification protein (TUM1). The role of the human TUM1 protein has been suggested in a wide range of physiological processes in the cell among which are but not limited to involvement in Molybdenum cofactor (Moco) biosynthesis, cytosolic tRNA thiolation and generation of H2S as signaling molecule both in mitochondria and the cytosol. Previous interaction studies showed that TUM1 interacts with the L-cysteine desulfurase NFS1 and the Molybdenum cofactor biosynthesis protein 3 (MOCS3). Here, we show the roles of TUM1 in human cells using CRISPR/Cas9 genetically modified Human Embryonic Kidney cells. Here, we show that TUM1 is involved in the sulfur transfer for Molybdenum cofactor synthesis and tRNA thiomodification by spectrophotometric measurement of the activity of sulfite oxidase and liquid chromatography quantification of the level of sulfur-modified tRNA. Further, we show that TUM1 has a role in hydrogen sulfide production and cellular bioenergetics.


Assuntos
Cofatores de Molibdênio , Sulfurtransferases , Humanos , Citosol/metabolismo , Sulfurtransferases/metabolismo , Metabolismo Energético , Enxofre/metabolismo , RNA de Transferência/metabolismo , Rim/metabolismo , Liases de Carbono-Enxofre/metabolismo
3.
Acta Crystallogr D Struct Biol ; 79(Pt 1): 22-30, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36601804

RESUMO

Friedreich's ataxia (FRDA) is a hereditary cardiodegenerative and neurodegenerative disease that affects 1 in 50 000 Americans. FRDA arises from either a cellular inability to produce sufficient quantities or the production of a nonfunctional form of the protein frataxin, a key molecule associated with mitochondrial iron-sulfur cluster biosynthesis. Within the mitochondrial iron-sulfur cluster (ISC) assembly pathway, frataxin serves as an allosteric regulator for cysteine desulfurase, the enzyme that provides sulfur for [2Fe-2S] cluster assembly. Frataxin is a known iron-binding protein and is also linked to the delivery of ferrous ions to the scaffold protein, the ISC molecule responsible for the direct assembly of [2Fe-2S] clusters. The goal of this report is to provide structural details of the Drosophila melanogaster frataxin ortholog (Dfh), using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, in order to provide the foundational insight needed to understand the structure-function correlation of the protein. Additionally, NMR iron(II) titrations were used to provide metal contacts on the protein to better understand how it binds iron and aids its delivery to the ISC scaffold protein. Here, the structural and functional similarities of Dfh to its orthologs are also outlined. Structural data show that bacterial, yeast, human and Drosophila frataxins are structurally similar, apart from a structured C-terminus in Dfh that is likely to aid in protein stability. The iron-binding location on helix 1 and strand 1 of Dfh is also conserved across orthologs.


Assuntos
Drosophila melanogaster , Doenças Neurodegenerativas , Animais , Humanos , Drosophila melanogaster/metabolismo , Proteínas de Ligação ao Ferro/química , Proteínas de Ligação ao Ferro/metabolismo , Saccharomyces cerevisiae/metabolismo , Ferro/metabolismo , Enxofre/metabolismo
4.
Huan Jing Ke Xue ; 44(1): 512-519, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635839

RESUMO

Soil microorganisms dominate the biogeochemical cycles of elements in glacier forelands, which continue to expand due to the climate warming. We analyzed the soil microbial functional characteristics among three types of glacier forelands on the Tibetan Plateau: Yulong Glacier (Y), a temperate glacier; Tianshan Urumqi Glacier No.1 (T), a sub-continental glacier; and Laohugou Glacier No.12 (L), a continental glacier. Here, soil microbial functional genes were quantified using quantitative microbial element cycling technology (QMEC). We found that, in the three glacier forelands, the abundances of soil microbial functional genes related to hemicellulose degradation and reductive acetyl-CoA pathway were highest compared with other carbon-related functional genes. The main nitrogen cycling genes were involved in ammonification. The functional genes of the phosphorus cycle and sulfur cycle were related to organic phosphate mineralization and sulfur oxidation. Furthermore, the soils of the temperate glacier foreland with better hydrothermal conditions had the most complex microbial functional gene structure and the highest functional potentials, followed by those of the soils of continental glacier foreland with the driest environment. These significant differences in soil microbial functional genes among the three types of glacier forelands verified the impacts of geographic difference on microbial functional characteristics, as well as providing a basis for the study of soil microbial functions and biogeochemical cycles in glacier forelands.


Assuntos
Camada de Gelo , Microbiologia do Solo , Tibet , Camada de Gelo/química , Solo/química , Enxofre/metabolismo
5.
New Phytol ; 237(1): 78-87, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226797

RESUMO

Sulfur (S) is an essential macronutrient for plants and a signaling molecule in abiotic stress responses. It is known that S availability modulates root system architecture; however, the underlying molecular mechanisms are largely unknown. We previously reported an Arabidopsis gain-of-function mutant sulfate utilization efficiency4 (sue4) that could tolerate S deficiency during germination and early seedling growth with faster primary root elongation. Here, we report that SUE4, a novel plasma membrane-localized protein, interacts with the polar auxin transporter PIN1, resulting in reduced PIN1 protein levels and thus decreasing auxin transport to the root tips, which promotes primary root elongation. Moreover, SUE4 is induced by sulfate deficiency, consistent with its role in root elongation. Further analyses showed that the SUE4-PIN1 interaction decreased PIN1 levels, possibly through 26 S proteasome-mediated degradation. Taken together, our finding of SUE4-mediated root elongation is consistent with root adaptation to highly mobile sulfate in soil, thus revealing a novel component in the adaptive response of roots to S deficiency.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Proteínas de Membrana/metabolismo , Raízes de Plantas/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transporte Biológico , Enxofre/metabolismo , Sulfatos/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo
6.
J Agric Food Chem ; 71(1): 398-410, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36574335

RESUMO

Soybean is a major source of high-quality protein for humans and animals. The content of sulfur-containing amino acids (SAA) in soybean is insufficient, which has become the main factor limiting soybean nutrition. In this study, we used the high-density genetic maps derived from Guizao 1 and Brazil 13 to evaluate the quantitative trait loci of cysteine (Cys), methionine (Met), SAA, glycinin (7S), ß-conglycinin (11S), ratio of glycinin to ß-conglycinin (RGC), and protein content (PC). In genetic map linkage analysis, the major and stable 44 QTLs were detected, which shared nine bin intervals. Among them, the bin interval (bin157-bin160) on chromosome 5 was detected in multiple environments as a stable QTL, which was linked to 11S, 7S, RGC, and SSA. Based on the analysis of bioinformatics and RNA-sequencing data, 16 differentially expressed genes (DEGs) within these QTLs were selected as candidate genes. These results will help to elucidate the genetic mechanism of soybean SAA-related traits and provide the basis for the gene mining of sulfur-containing amino acids.


Assuntos
Locos de Características Quantitativas , Soja , Humanos , Soja/genética , Soja/metabolismo , Aminoácidos/metabolismo , Mapeamento Cromossômico/métodos , Fenótipo , Enxofre/metabolismo , Sementes/química
7.
Biomaterials ; 293: 121987, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36584445

RESUMO

Various cancer cells overexpress L-type amino acid transporter 1 (LAT1) to take up a large number of neutral amino acids such as phenylalanine and methionine, and LAT1 transporter should be a promising target for cancer diagnosis and therapy. However, only a few studies reported drug delivery systems targeting LAT1 probably due to limited knowledge about the interaction between LAT1 and its substrate. Here, we developed polymers having methionine (Met)- or cysteine (Cys)-like structures on their side chains to examine their affinity with LAT1. While both the Met- and Cys-modified polymers exhibited efficient cellular uptake selectively in cancer cells, the Met-modified polymers exhibited higher cellular uptake efficiency in an LAT1-selective manner than the Cys-modified polymers. In the in vivo study, the intraperitoneally injected Met-modified polymers showed appreciable tumor-selective accumulation in the peritoneal dissemination model, and importantly, Met-modified polymers conjugated with photosensitizers exhibited significant therapeutic effects upon photoirradiation with reduced photochemical damage to normal organs. Our results may provide important knowledge about the polymer-LAT1 interaction, and the Met-modified polymers should offer a new concept for designing LAT1-targeting drug delivery systems.


Assuntos
Aminoácidos , Neoplasias , Humanos , Neoplasias/metabolismo , Metionina/metabolismo , Racemetionina , Sistemas de Transporte de Aminoácidos , Polímeros/metabolismo , Enxofre/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo
8.
Sci Total Environ ; 862: 160930, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36526186

RESUMO

The mangrove ecosystem has a high nitrate reduction capacity, which significantly alleviates severe nitrogen pollution. However, current research on nitrate reduction mechanisms in the mangrove ecosystem is limited. Furthermore, Spartina alterniflora invasion has disrupted the balance of the mangrove ecosystem and the effect of S. alterniflora on nitrate reduction has not yet been fully elucidated. Nitrate reduction was comprehensively investigated in a subtropical mangrove ecosystem in this study, which has been invaded by S. alterniflora for 40 years. Results showed that S. alterniflora significantly increased the relative and absolute abundance of nitrate reduction genes, especially nirS (nitrite reductase), in the mangrove ecosystem. Dissimilatory nitrate reduction to ammonium was the main pathway of nitrate reduction in the mangrove ecosystem. Nitrate reduction was mainly performed by Desulfobacterales and occurred in the shallow layers (0-10 cm) of mangrove sediments. A strong positive correlation was found between nitrate reduction and sulfur oxidation (especially sulfide oxidation), and the sulfide content was significantly positively correlated with the relative abundance of nitrate reduction genes. Moreover, 207 metagenomic assembled genomes (MAGs) were constructed, including 50 MAGs with high numbers (≥ 10) of nitrate reduction genes. This finding indicates that the dominant microbes had strong nitrate reduction potential in mangrove sediments. Our findings highlight the impact of S. alterniflora invasion on nitrate reduction in a subtropical marine mangrove ecosystem. This study provides new insights into our understanding of nitrogen pollution control and contributes to the exploration of new nitrogen-degrading microbes in mangrove ecosystems.


Assuntos
Ecossistema , Áreas Alagadas , Nitratos/metabolismo , Espécies Introduzidas , Poaceae/metabolismo , Nitrogênio/análise , Enxofre/metabolismo , China
9.
Sci Total Environ ; 865: 161193, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36581268

RESUMO

Anaerobic digestion (AD) is an economical and environment-friendly technology for treating organic solid wastes (OSWs). OSWs with high sulfur can lead to the accumulation of toxic and harmful hydrogen sulfide (H2S) during AD, so a considerable amount of studies have focused on removing H2S emissions. However, current studies have found that sulfide induces phosphate release from the sludge containing iron­phosphorus compounds (FePs) and the feasibility of recovering elemental sulfur (S0) during AD. To tap the full potential of sulfur in OSWs resource recovery, deciphering the sulfur transformation pathway and its influencing factors is required. Therefore, in this review, the sulfur species and distributions in OSWs and the pathway of sulfur transformation during AD were systematically summarized. Then, the relationship between iron (ferric compounds and zero-valent iron), phosphorus (FePs) and sulfur were analyzed. It was found that the reaction of iron with sulfide during AD drove the conversion of sulfide to S0 and iron sulfide compounds (FeSx), and consequently iron was applied in sulfide abatement. In particular, ferric (hydr)oxide granules offer possibilities to improve the economic viability of hydrogen sulfide control by recovering S0. Sulfide is an interesting strategy to release phosphate from the sludge containing FePs for phosphorus recovery. Critical factors affecting sulfur transformation, including the carbon source, free ammonia and pretreatment methods, were summarized and discussed. Carbon source and free ammonia affected sulfur-related microbial diversity and enzyme activity and different sulfur transformation pathways in response to varying pretreatment methods. The study on S0 recovery, organic sulfur conversion, and phosphate release mechanism triggered by sulfur deserves further investigation. This review is expected to enrich our knowledge of the role of sulfur during AD and inspire new ideas for recovering phosphorus and sulfur resources from OSWs.


Assuntos
Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/análise , Esgotos , Resíduos Sólidos/análise , Anaerobiose , Amônia , Sulfetos , Ferro , Fósforo , Fosfatos , Enxofre/metabolismo
10.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499175

RESUMO

Malus is an economically important plant that is widely cultivated worldwide, but it often encounters saline-alkali stress. The composition of saline-alkali land is a variety of salt and alkali mixed with the formation of alkaline salt. Hydrogen sulfide (H2S) has been reported to have positive effects on plant responses to abiotic stresses. Our previous study showed that H2S pretreatment alleviated the damage caused by alkaline salt stress to Malus hupehensis Rehd. var. pingyiensis Jiang (Pingyi Tiancha, PYTC) roots by regulating Na+/K+ homeostasis and oxidative stress. In this study, transcriptome analysis was used to investigate the overall mechanism through which H2S alleviates alkaline salt stress in PYTC roots. Simultaneously, differentially expressed genes (DEGs) were explored. Transcriptional profiling of the Control-H2S, Control-AS, Control-H2S + AS, and AS-H2S + AS comparison groups identified 1618, 18,652, 16,575, and 4314 DEGs, respectively. Further analysis revealed that H2S could alleviate alkaline salt stress by increasing the energy maintenance capacity and cell wall integrity of M. hupehensis roots and by enhancing the capacity for reactive oxygen species (ROS) metabolism because more upregulated genes involved in ROS metabolism and sulfur-containing compounds were identified in M. hupehensis roots after H2S pretreatment. qRT-PCR analysis of H2S-induced and alkaline salt-response genes showed that these genes were consistent with the RNA-seq analysis results, which indicated that H2S alleviation of alkaline salt stress involves the genes of the cell wall and sulfur-containing compounds in PYTC roots.


Assuntos
Malus , Malus/genética , Compostos de Enxofre/metabolismo , Raízes de Plantas/metabolismo , Estresse Fisiológico/genética , Estresse Salino/genética , Parede Celular/metabolismo , Enxofre/metabolismo , Regulação da Expressão Gênica de Plantas
11.
Microbiome ; 10(1): 235, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566239

RESUMO

BACKGROUND: The deep sea harbors many viruses, yet their diversity and interactions with hosts in hydrothermal ecosystems are largely unknown. Here, we analyzed the viral composition, distribution, host preference, and metabolic potential in different habitats of global hydrothermal vents, including vent plumes, background seawater, diffuse fluids, and sediments. RESULTS: From 34 samples collected at eight vent sites, a total of 4662 viral populations (vOTUs) were recovered from the metagenome assemblies, encompassing diverse phylogenetic groups and defining many novel lineages. Apart from the abundant unclassified viruses, tailed phages are most predominant across the global hydrothermal vents, while single-stranded DNA viruses, including Microviridae and small eukaryotic viruses, also constitute a significant part of the viromes. As revealed by protein-sharing network analysis, hydrothermal vent viruses formed many novel genus-level viral clusters and are highly endemic to specific vent sites and habitat types. Only 11% of the vOTUs can be linked to hosts, which are the key microbial taxa of hydrothermal habitats, such as Gammaproteobacteria and Campylobacterota. Intriguingly, vent viromes share some common metabolic features in that they encode auxiliary genes that are extensively involved in the metabolism of carbohydrates, amino acids, cofactors, and vitamins. Specifically, in plume viruses, various auxiliary genes related to methane, nitrogen, and sulfur metabolism were observed, indicating their contribution to host energy conservation. Moreover, the prevalence of sulfur-relay pathway genes indicated the significant role of vent viruses in stabilizing the tRNA structure, which promotes host adaptation to steep environmental gradients. CONCLUSIONS: The deep-sea hydrothermal systems hold untapped viral diversity with novelty. They may affect both vent prokaryotic and eukaryotic communities and modulate host metabolism related to vent adaptability. More explorations are needed to depict global vent virus diversity and its roles in this unique ecosystem. Video Abstract.


Assuntos
Fontes Hidrotermais , Vírus , Ecossistema , Filogenia , Fontes Hidrotermais/microbiologia , Vírus/genética , Vírus/metabolismo , Enxofre/metabolismo
12.
Microbiome ; 10(1): 241, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36572924

RESUMO

BACKGROUND: When deep-sea hydrothermal fluids mix with cold oxygenated fluids, minerals precipitate out of solution and form hydrothermal deposits. These actively venting deep-sea hydrothermal deposits support a rich diversity of thermophilic microorganisms which are involved in a range of carbon, sulfur, nitrogen, and hydrogen metabolisms. Global patterns of thermophilic microbial diversity in deep-sea hydrothermal ecosystems have illustrated the strong connectivity between geological processes and microbial colonization, but little is known about the genomic diversity and physiological potential of these novel taxa. Here we explore this genomic diversity in 42 metagenomes from four deep-sea hydrothermal vent fields and a deep-sea volcano collected from 2004 to 2018 and document their potential implications in biogeochemical cycles. RESULTS: Our dataset represents 3635 metagenome-assembled genomes encompassing 511 novel and recently identified genera from deep-sea hydrothermal settings. Some of the novel bacterial (107) and archaeal genera (30) that were recently reported from the deep-sea Brothers volcano were also detected at the deep-sea hydrothermal vent fields, while 99 bacterial and 54 archaeal genera were endemic to the deep-sea Brothers volcano deposits. We report some of the first examples of medium- (≥ 50% complete, ≤ 10% contaminated) to high-quality (> 90% complete, < 5% contaminated) MAGs from phyla and families never previously identified, or poorly sampled, from deep-sea hydrothermal environments. We greatly expand the novel diversity of Thermoproteia, Patescibacteria (Candidate Phyla Radiation, CPR), and Chloroflexota found at deep-sea hydrothermal vents and identify a small sampling of two potentially novel phyla, designated JALSQH01 and JALWCF01. Metabolic pathway analysis of metagenomes provides insights into the prevalent carbon, nitrogen, sulfur, and hydrogen metabolic processes across all sites and illustrates sulfur and nitrogen metabolic "handoffs" in community interactions. We confirm that Campylobacteria and Gammaproteobacteria occupy similar ecological guilds but their prevalence in a particular site is driven by shifts in the geochemical environment. CONCLUSION: Our study of globally distributed hydrothermal vent deposits provides a significant expansion of microbial genomic diversity associated with hydrothermal vent deposits and highlights the metabolic adaptation of taxonomic guilds. Collectively, our results illustrate the importance of comparative biodiversity studies in establishing patterns of shared phylogenetic diversity and physiological ecology, while providing many targets for enrichment and cultivation of novel and endemic taxa. Video Abstract.


Assuntos
Fontes Hidrotermais , Microbiota , Humanos , Fontes Hidrotermais/microbiologia , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Bactérias , Archaea , Microbiota/genética , Enxofre/metabolismo , Carbono/metabolismo , Nitrogênio/metabolismo , Hidrogênio/metabolismo
13.
Oxid Med Cell Longev ; 2022: 7449941, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338346

RESUMO

Iron-sulfur clusters are ancient cofactors that play crucial roles in myriad cellular functions. Recent studies have shown that iron-sulfur clusters are closely related to the mechanisms of multiple cell death modalities. In addition, numerous previous studies have demonstrated that iron-sulfur clusters play an important role in the development and treatment of cancer. This review first summarizes the close association of iron-sulfur clusters with cell death modalities such as ferroptosis, cuprotosis, PANoptosis, and apoptosis and their potential role in cancer activation and drug resistance. This review hopes to generate new cancer therapy ideas and overcome drug resistance by modulating iron-sulfur clusters.


Assuntos
Proteínas Ferro-Enxofre , Neoplasias , Humanos , Ferro/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Enxofre/metabolismo , Apoptose
14.
Biochemistry ; 61(23): 2733-2741, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36351081

RESUMO

Iron-sulfur (Fe-S) cluster (ISC) cofactors are required for the function of many critical cellular processes. In the ISC Fe-S cluster biosynthetic pathway, IscU assembles Fe-S cluster intermediates from iron, electrons, and inorganic sulfur, which is provided by the cysteine desulfurase enzyme IscS. IscU also binds to Zn, which mimics and competes for binding with the Fe-S cluster. Crystallographic and nuclear magnetic resonance spectroscopic studies reveal that IscU is a metamorphic protein that exists in multiple conformational states, which include at least a structured form and a disordered form. The structured form of IscU is favored by metal binding and is stable in a narrow temperature range, undergoing both cold and hot denaturation. Interestingly, the form of IscU that binds IscS and functions in Fe-S cluster assembly remains controversial. Here, results from variable temperature electrospray ionization (vT-ESI) native ion mobility mass spectrometry (nIM-MS) establish that IscU exists in structured, intermediate, and disordered forms that rearrange to more extended conformations at higher temperatures. A comparison of Zn-IscU and apo-IscU reveals that Zn(II) binding attenuates the cold/heat denaturation of IscU, promotes refolding of IscU, favors the structured and intermediate conformations, and inhibits the disordered high charge states. Overall, these findings provide a structural rationalization for the role of Zn(II) in stabilizing IscU conformations and IscS in altering the IscU active site to prepare for Zn(II) release and cluster synthesis. This work highlights how vT-ESI-nIM-MS can be applied as a powerful tool in mechanistic enzymology by providing details of relationships among temperature, protein conformations, and ligand/protein binding.


Assuntos
Proteínas de Escherichia coli , Proteínas Ferro-Enxofre , Proteínas Ferro-Enxofre/química , Temperatura , Espectrometria de Massas por Ionização por Electrospray , Liases de Carbono-Enxofre/metabolismo , Enxofre/metabolismo , Ferro/química , Proteínas de Escherichia coli/química
15.
Cells ; 11(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36359860

RESUMO

Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease. Iron transport in and out of the cell and cellular organelles is crucial in this regard. The transport of iron into the mitochondria is particularly important, as heme and the majority of iron-sulfur clusters are synthesized in this organelle. Iron is also required for the production of mitochondrial complexes that contain these iron-sulfur clusters and heme. As the principal iron importers in the mitochondria of human cells, the mitoferrins have emerged as critical regulators of cytosolic and mitochondrial iron homeostasis. Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.


Assuntos
Heme , Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Homeostase , Heme/metabolismo , Ferro/metabolismo , Enxofre/metabolismo
16.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362080

RESUMO

1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H2S) using RSS-specific fluorophores, liquid chromatography-mass spectrometry, UV-Vis absorption spectrometry, oxygen-sensitive optodes, thiosulfate-specific nanoparticles, HPLC-monobromobimane derivatization, and ion chromatographic assays. We show that NQs, catalytically oxidize H2S to per- and polysulfides (H2Sn, n = 2-6), thiosulfate, sulfite and sulfate in reactions that consume oxygen and are accelerated by superoxide dismutase (SOD) and inhibited by catalase. The approximate efficacy of NQs (in decreasing order) is, 1,4-NQ ≈ juglone ≈ plumbagin > 2-methoxy-1,4-NQ ≈ menadione >> phylloquinone ≈ anthraquinone ≈ menaquinone ≈ lawsone. We propose that the most probable reactions are an initial two-electron oxidation of H2S to S0 and reduction of NQ to NQH2. S0 may react with H2S or elongate H2Sn in variety of reactions. Reoxidation of NQH2 likely involves a semiquinone radical (NQ·-) intermediate via several mechanisms involving oxygen and comproportionation to produce NQ and superoxide. Dismutation of the latter forms hydrogen peroxide which then further oxidizes RSS to sulfoxides. These findings provide the chemical background for novel sulfur-based approaches to naphthoquinone-directed therapies.


Assuntos
Sulfeto de Hidrogênio , Naftoquinonas , Tiossulfatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Oxirredução , Naftoquinonas/farmacologia , Naftoquinonas/metabolismo , Sulfeto de Hidrogênio/metabolismo , Enxofre/metabolismo , Oxigênio/metabolismo
17.
Mol Microbiol ; 118(4): 387-402, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36271735

RESUMO

Repairing oxidative-targeted macromolecules is a central mechanism necessary for living organisms to adapt to oxidative stress. Reactive oxygen and chlorine species preferentially oxidize sulfur-containing amino acids in proteins. Among these amino acids, methionine can be converted into methionine sulfoxide. This post-translational oxidation can be reversed by methionine sulfoxide reductases, Msr enzymes. In Gram-negative bacteria, the antioxidant MsrPQ system is involved in the repair of periplasmic oxidized proteins. Surprisingly, in this study, we observed in Escherichia coli that msrPQ was highly expressed in the absence of oxygen. We have demonstrated that the anaerobic induction of msrPQ was due to chlorate (ClO3 - ) contamination of the Casamino Acids. Molecular investigation led us to determine that the reduction of chlorate to the toxic oxidizing agent chlorite (ClO2 - ) by the three nitrate reductases (NarA, NarZ, and Nap) led to methionine oxidation of periplasmic proteins. In response to this stress, the E. coli HprSR two-component system was activated, leading to the over-production of MsrPQ. This study, therefore, supports the idea that methionine oxidation in proteins is part of chlorate toxicity, and that MsrPQ can be considered as an anti-chlorate/chlorite defense system in bacteria. Finally, this study challenges the traditional view of the absence of Met-oxidation during anaerobiosis.


Assuntos
Escherichia coli , Proteínas Periplásmicas , Escherichia coli/metabolismo , Metionina Sulfóxido Redutases/metabolismo , Proteínas Periplásmicas/metabolismo , Anaerobiose , Cloro/metabolismo , Antioxidantes/metabolismo , Oxirredução , Metionina/metabolismo , Racemetionina/metabolismo , Oxigênio/metabolismo , Oxidantes/metabolismo , Enxofre/metabolismo
18.
Front Cell Infect Microbiol ; 12: 639624, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237423

RESUMO

Peritoneal dialysis (PD) is a renal replacement therapy for end-stage renal disease. Gut microbiota-derived uremic solutes, indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine-N-oxide (TMAO) accumulate in PD patients. The objective was to explore the gut microbiota and their influence on uremic toxins in PD patients and healthy controls (HC). Fecal samples were collected from PD patients (n = 105) and HC (n = 102). 16S rRNA gene regions were sequenced for gut microbiota analysis. IS, PCS, and TMAO levels were measured using HPLC-MS. PD patients exhibited lower alpha diversity and altered gut microbiota composition compared to HC. At the genus level, PD patients showed increased abundance of opportunistic pathogenic bacteria, and decreased abundance of beneficial bacteria. Three Operational Taxonomic Units discriminated PD patients from HC. Phenylalanine metabolism increased in PD, whereas tryptophan metabolism was unaltered. Low serum PCS did not necessarily mean healthier due to the loss of alpha diversity, increased Proteobacteria and opportunistic pathogenic bacteria. High serum PCS was mainly caused by elevated p-cresol-producing bacteria, enriched amino acid related enzymes, and enhanced sulfur metabolism, rather than declined residual renal function. In patients with different urine volumes, the gut microbiota alpha diversity and composition were unaltered, but serum IS and TMAO were significantly elevated in anuric patients. In conclusion, the gut microbiota abundance, composition, and function were altered in PD patients, which increased the PCS levels. We provided a better understanding of the microbiota-metabolite-kidney axis in PD patients. Targeting certain bacteria could decrease the PCS levels, whereas preserving the residual renal function could reduce the IS and TMAO levels.


Assuntos
Microbioma Gastrointestinal , Diálise Peritoneal , Bactérias/genética , Bactérias/metabolismo , Humanos , Indicã/metabolismo , Metilaminas , Óxidos/metabolismo , Fenilalanina/metabolismo , RNA Ribossômico 16S/genética , Sulfatos/metabolismo , Enxofre/metabolismo , Triptofano/metabolismo
19.
Methods Enzymol ; 676: 197-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36280350

RESUMO

Sulfur metabolism provides a number of compounds that are essential for plant survival and fitness and that affect the yield and quality of crops. Sulfur metabolism is a dynamic process, responding to a number of external cues. Because of this dynamics and rapid turnover, steady-state levels of sulfur-containing compounds do not always fully reflect plant responses to such cues. Therefore, measurements of the flux through sulfate assimilation may give a more precise estimate of the effects of environmental stimuli or metabolic disturbances on sulfur metabolism. The flux can be determined after feeding plants with sulfate labelled with an isotopic tracer. Here we describe a protocol for using [35S]sulfate to measure flux through sulfate assimilation in Arabidopsis. The protocol can be adapted for any plant species and growth conditions, and does not require any special equipment beyond a standard high performance liquid chromatograph. We hope that the protocol will support our colleagues in a more frequent use of flux measurements to answer new biological questions in plant sulfur metabolism.


Assuntos
Arabidopsis , Sulfatos , Sulfatos/metabolismo , Enxofre/metabolismo , Arabidopsis/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
20.
Nat Metab ; 4(10): 1260-1270, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36266544

RESUMO

Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H2S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H2S accumulation in vivo. Cryptic H2S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.


Assuntos
Sulfeto de Hidrogênio , Microbiota , Humanos , Masculino , Camundongos , Animais , Sulfeto de Hidrogênio/metabolismo , Xenobióticos/metabolismo , Bactérias/metabolismo , Oxirredução , Sulfetos/metabolismo , Enxofre/metabolismo , Compostos Azo/metabolismo , Escherichia coli/metabolismo , Corantes/metabolismo
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