RESUMEN
Acetobacter is one of the main species producing fruit vinegar and its tolerance mechanism to citric acid has not been fully studied. This limits fruit vinegar production from high-citric-acid fruits, which are excellent materials for fruit vinegar production. This study analyzed the metabolic differences between two strains of A. tropicalis with different citric acid tolerances using non-targeted metabolomics. Differential metabolites and metabolic pathways analysis showed that the enhanced amino acid metabolism significantly improved the citric acid tolerance of A. tropicalis and the deamination of amino acids may also play a role. In addition, the up-regulated phosphatidylcholine (PC) and N-heptanoylhonoserine lactone indicated decreased membrane permeability and enhanced quorum sensing (QS), respectively. The analysis of the interaction between pathways and metabolites indicated that Gln, Cys, and Tyr contribute to improving citric acid tolerance, which was also confirmed by the exogenous addition. After adding the amino acids, the down-regulated qdh, up-regulated ggt, and improved glutathione reductase (GR) activity in J-2736 indicated that glutathione metabolism played an important role in resisting citric acid, and cellular antioxidant capacity was increased. This study provides a theoretical basis for efficient fruit vinegar production from citric-acid-type fruits.
Asunto(s)
Ácido Acético , Acetobacter , Antioxidantes , Ácido Cítrico , Glutatión , Acetobacter/metabolismo , Acetobacter/efectos de los fármacos , Ácido Cítrico/metabolismo , Ácido Acético/metabolismo , Ácido Acético/farmacología , Antioxidantes/metabolismo , Glutatión/metabolismo , Frutas/microbiología , Frutas/metabolismo , Aminoácidos/metabolismo , Percepción de Quorum , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Metabolómica , Redes y Vías MetabólicasRESUMEN
Fusarium verticillioides is both an endophyte and pathogen of maize. During growth on maize, the fungus often synthesizes the mycotoxins fumonisins, which have been linked to a variety of diseases, including cancer in some animals. How F. verticillioides responds to other fungi, such as Fusarium proliferatum, Aspergillus flavus, Aspergillus niger, and Penicillium oxalicum, that coinfect maize, has potential to impact mycotoxin synthesis and disease. We hypothesize that low molecular weight acids produced by these fungi play a role in communication between the fungi in planta/nature. To address this hypothesis, we exposed 48-h maize kernel cultures of F. verticillioides to oxalic acid, citric acid, fusaric acid, or kojic acid and then compared transcriptomes after 30 min and 6 h. Transcription of some genes were affected by multiple chemicals and others were affected by only one chemical. The most significant positive response was observed after exposure to fusaric acid which resulted in >2-fold upregulation of 225 genes, including genes involved in fusaric acid synthesis. Exposure of cultures to the other three chemicals increased expression of only 3-15 genes. The predicted function and frequent co-localization of three sets of genes support a role in protecting the fungus from the chemical or a role in catabolism. These unique transcriptional responses support our hypothesis that these chemicals can act as signaling molecules. Studies with gene deletion mutants will further indicate if the initial transcriptional response to the chemicals benefit F. verticillioides.
Asunto(s)
Ácido Fusárico , Fusarium , Zea mays , Fusarium/genética , Fusarium/metabolismo , Fusarium/efectos de los fármacos , Fusarium/crecimiento & desarrollo , Zea mays/microbiología , Ácido Fusárico/farmacología , Ácido Fusárico/metabolismo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Pironas/farmacología , Pironas/metabolismo , Ácido Cítrico/metabolismo , Ácido Cítrico/farmacología , Ácido Oxálico/metabolismo , Perfilación de la Expresión Génica , Transcripción GenéticaRESUMEN
Human acetyl-coenzyme A (CoA) carboxylases (ACCs) catalyze the carboxylation of acetyl-CoA, which is the rate-limiting step in fatty acid synthesis. The molecular mechanism underlying the dynamic organization of ACCs is largely unknown. Here, we determined the cryo-electron microscopy (EM) structure of human ACC1 in its inactive state, which forms a unique filament structure and is in complex with acetyl-CoA. We also determined the cryo-EM structure of human ACC1 activated by dephosphorylation and citrate treatment, at a resolution of 2.55 Å. Notably, the covalently linked biotin binds to a site that is distant from the acetyl-CoA binding site when acetyl-CoA is absent, suggesting a potential coordination between biotin binding and acetyl-CoA binding. These findings provide insights into the structural dynamics and regulatory mechanisms of human ACCs.
Asunto(s)
Acetilcoenzima A , Acetil-CoA Carboxilasa , Microscopía por Crioelectrón , Modelos Moleculares , Humanos , Acetil-CoA Carboxilasa/metabolismo , Acetil-CoA Carboxilasa/química , Acetilcoenzima A/metabolismo , Acetilcoenzima A/química , Sitios de Unión , Unión Proteica , Biotina/química , Biotina/metabolismo , Fosforilación , Conformación Proteica , Ácido Cítrico/química , Ácido Cítrico/metabolismoRESUMEN
The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has biological toxicity, persistence, long-range migration and bioaccumulation ability. However, there is currently little research on the phytotoxicity of DBDPE in plants. The perennial herbaceous plant tall fescue (Festuca elata Keng ex E. B. Alexeev) was selected as the model organism for use in seed germination experiments, and the phytotoxicity of DBDPE in the soil of tall fescue was studied. The results indicated that DBDPE had a significant effect on the germination and growth of tall fescue seedlings. Citric acid reduced the stress caused by DBDPE in plants, effectively alleviating the phytotoxicity of DBDPE in tall fescue. The root vitality and protein content significantly increased after the application of citric acid, increasing by 74.93-183.90%, 146.44-147.67%, respectively. The contents of proline and soluble sugars significantly decreased after the application of citric acid, decreasing by 45.18-59.69% and 23.03%, respectively (P < 0.05). There was no significant difference in superoxide dismutase (SOD) or peroxidase (POD) activity in tall fescue seedlings, and the catalase (CAT) activity and malondialdehyde (MDA) content were significantly lower after the application of citric acid, decreasing by 64.62-67.91% and 29.10-49.80%, respectively (P < 0.05). Tall fescue seedlings bioaccumulated DBDPE, with biological concentration factors (BCFs) ranging from 4.28 to 18.38 and transfer factors (TFs) ranging from 0.43 to 0.54. This study provides theoretical support for the study of the toxicity of DBDPE to plants and offers a research foundation for exploring the phytoremediation of DBDPE-contaminated soil by tall fescue.
Asunto(s)
Ácido Cítrico , Festuca , Germinación , Plantones , Contaminantes del Suelo , Plantones/metabolismo , Plantones/efectos de los fármacos , Festuca/metabolismo , Festuca/efectos de los fármacos , Ácido Cítrico/metabolismo , Germinación/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Bromobencenos/toxicidad , Retardadores de Llama/toxicidad , Retardadores de Llama/metabolismo , Semillas/efectos de los fármacos , Semillas/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacosRESUMEN
Mortierella alpina is popular for lipid production, but the low carbon conversion rate and lipid yield are major obstacles for its economic performance. Here, external addition of organic acids involved in tricarboxylic acid cycle was used to tune carbon flux and improve lipid production. Citrate was determined to be the best organic acid that can be used for enhancing lipid production. By the addition of citrate, the lipid titer and content were approximately 1.24 and 1.34 times higher, respectively. Meanwhile, citrate supplement also promoted the accumulation of succinate, an important value-added platform chemical. Owing to the improved lipid and succinate production through adding citrate, the carbon conversion rate of M. alpina reached up to 52.17%, much higher than that of the control group (14.11%). The addition of citrate could redistribute carbon flux by regulating the expression level of genes related to tricarboxylic acid cycle metabolism. More carbon fluxes flow to lipid and succinate synthesis, which greatly improved the carbon conversion efficiency of M. alpina. This study provides an effective and straightforward strategy with potential economic benefits to improve carbon conversion efficiency in M. alpina.
Asunto(s)
Carbono , Ciclo del Ácido Cítrico , Ácido Cítrico , Mortierella , Ácido Succínico , Mortierella/metabolismo , Mortierella/genética , Ácido Succínico/metabolismo , Carbono/metabolismo , Ácido Cítrico/metabolismo , Lípidos/biosíntesis , Metabolismo de los Lípidos , Regulación Fúngica de la Expresión Génica , FermentaciónRESUMEN
Methanol reportedly stimulates citric acid (CA) production by Aspergillus niger and A. tubingensis; however, the underlying mechanisms remain unclear. Here, we elucidated the molecular functions of the citrate exporter gene cexA in relation to CA production by A. tubingensis WU-2223L. Methanol addition to the medium containing glucose as a carbon source markedly increased CA production by strain WU-2223L by 3.38-fold, resulting in a maximum yield of 65.5 g/L, with enhanced cexA expression. Conversely, the cexA-complementing strain with the constitutive expression promoter Ptef1 (strain LhC-1) produced 68.3 or 66.7 g/L of CA when cultivated without or with methanol, respectively. Additionally, strain LhC-2 harboring two copies of the cexA expression cassette produced 80.7 g/L of CA without methanol addition. Overall, we showed that cexA is a target gene for methanol in CA hyperproduction by A. tubingensis WU-2223L. Based on these findings, methanol-independent CA-hyperproducing strains, LhC-1 and LhC-2, were successfully generated.
Asunto(s)
Aspergillus , Ácido Cítrico , Metanol , Metanol/metabolismo , Ácido Cítrico/metabolismo , Aspergillus/genética , Aspergillus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regiones Promotoras Genéticas , Regulación Fúngica de la Expresión Génica , Fermentación , Glucosa/metabolismoRESUMEN
Sorghum seeds can discolor during storage. Treatment of seeds with citric acid improves sensory quality and antioxidant activity. This study compared the differences in phenotypic and antioxidant activity between citric acid-treated and water-treated sorghum seeds. The study used transcriptomics and metabolomics approaches to investigate the regulatory mechanisms. The ∆a, ∆b and ∆l values of citric acid-treated sorghum seeds significantly increased after 6 months of storage. The SOD, POD and CAT enzyme activities of the citric acid-treated group were 1.94, 1.91 and 2.45 times higher than those of the control, respectively. The joint transcriptome and metabolome analysis showed that the citric acid-induced changes were mainly focused on the flavonoid biosynthetic pathway. Citric acid treatment up-regulated CHS, ANR, MYB and bHLH genes and promoted flavonoid accumulation. In conclusion, citric acid treatment promotes flavonoid accumulation, delays sorghum seed discoloration, and enhances antioxidant activity and storage life.
Asunto(s)
Ácido Cítrico , Flavonoides , Semillas , Sorghum , Sorghum/metabolismo , Sorghum/química , Sorghum/genética , Flavonoides/metabolismo , Flavonoides/química , Ácido Cítrico/metabolismo , Semillas/química , Semillas/metabolismo , Semillas/genética , Antioxidantes/metabolismo , Antioxidantes/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Almacenamiento de AlimentosRESUMEN
Rahnella aquatilis causes seafoods to spoil by metabolizing sulfur-containing amino acids and/or proteins, producing H2S in products. The type II secretion system (T2SS) regulates the transport of proteases from the cytoplasm to the surrounding environment and promotes bacterial growth at low temperatures. To prevent premature fish spoilage, new solutions for inhibiting the T2SS of bacteria should be researched. In this study, global transcriptome sequencing was used to analyze the spoilage properties of R. aquatilis KM05. Two of the mapped genes/coding sequences (CDSs) were matched to the T2SS, namely, qspF and gspE, and four of the genes/CDSs, namely, ftsH, rseP, ptrA and pepN, were matched to metalloproteases or peptidases in R. aquatilis KM05. Subinhibitory concentrations of citric (18 µM) and acetic (41 µM) acids caused downregulation of T2SS-related genes (range from - 1.0 to -4.5) and genes involved in the proteolytic activities of bacteria (range from - 0.5 to -4.0). The proteolytic activities of R. aquatilis KM05 in vitro were reduced by an average of 40%. The in situ experiments showed the antimicrobial properties of citric and acetic acids against R. aquatilis KM05; the addition of an acidulant to salmon fillets limited microbial growth. Citric and acetic acids extend the shelf life of fish-based products and prevent food waste.
Asunto(s)
Ácido Cítrico , Rahnella , Alimentos Marinos , Animales , Ácido Cítrico/metabolismo , Alimentos Marinos/microbiología , Rahnella/genética , Rahnella/metabolismo , Salmón/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Ácido Acético/metabolismo , Ácido Acético/farmacología , Microbiología de Alimentos , Transcriptoma , Regulación Bacteriana de la Expresión GénicaRESUMEN
'Benihoppe' and 'Fenyu No.1' are representative varieties of red and pink strawberries in China, possess distinct hue and flavor profiles. This study analyzed the underlying biochemical and molecular differences of two varieties utilizing transcriptomics and high-performance liquid chromatography (HPLC). Ripening 'Benihoppe' fruits accumulated more sucrose and pelargonin-3-glucoside (P3G) with a little cyanidin and higher firmness. Whereas ripening 'Fenyu No.1' fruits contained more fructose, glucose, malic acid and ascorbic acid (AsA), but less P3G and citric acid. Moreover, genotype significantly influenced phenolic compounds contents in strawberries. Transcriptome analysis revealed that pectin degradation (PL, PG, PE), sucrose synthesis (CWINV, SUS, TPS) and citric acid metabolism (α-OGDH, ICDH, GAD, GS, GDH, PEPCK, AST) were weakened in 'Benihoppe' fruit. In contrast, the synthesis of sucrose (CWINH, SPS), citric acid (CS, PEPC), anthocyanin (F3H, F3'H, F3'5'H, DFR, UFGT and ANS), and citric acid transport (V-ATPase) was enhanced. In 'Fenyu No.1' fruit, the degradation of sucrose, citric acid, and pectin was enhanced, along with the synthesis of malic acid (ME) and ascorbic acid (PMM, MDHAR and GaLUR). However, anthocyanins synthesis, glucose metabolism (HK, G6PI, PFK, G6PDH, PGK, PGM, ENO, PK), fructose metabolism (FK), citric acid synthesis and transport, and AsA degradation (AO, APX) were relatively weak. RT-qPCR results corroborated the transcriptome data. In conclusion, this study revealed the distinctions and characteristics of strawberries with different fruit colors regarding texture, flavor and color formation processes. These findings offer valuable insights for regulating metabolic pathways and identifying key candidate genes to improve strawberry quality.
Asunto(s)
Fragaria , Frutas , Fragaria/genética , Fragaria/metabolismo , Cromatografía Líquida de Alta Presión , Frutas/metabolismo , Frutas/genética , Antocianinas/metabolismo , Antocianinas/biosíntesis , Transcriptoma/genética , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica/métodos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sacarosa/metabolismo , Ácido Ascórbico/metabolismo , Ácido Ascórbico/biosíntesis , Ácido Cítrico/metabolismoRESUMEN
Itaconic acid (IA) is one of the twelve high value-added platform compounds applied in various fields including coatings, adhesives, plastics, resins, and biofuels. In this study, we established a one-pot catalytic synthesis system for IA from citric acid based on the engineered salt-tolerant bacterial strain Halomonas bluephagenesis TDZI-08 after investigating factors that hindered the process and optimizing the carbon source, nitrogen source, inducer addition time, and surfactant dosage. The open, non-sterile, one-pot synthesis with TDZI-08 in a 5 L fermenter achieved the highest IA titer of 40.50 g/L, with a catalytic yield of 0.68 g IA/g citric acid during the catalytic stage and a total yield of 0.42 g IA/g (citric acid+gluconic acid). The one-pot synthesis system established in this study is simple and does not need sterilization or aseptic operations. The findings indicate the potential of H. bluephagenesis for industrial production of IA.
Asunto(s)
Halomonas , Succinatos , Halomonas/metabolismo , Halomonas/genética , Succinatos/metabolismo , Ingeniería Metabólica , Microbiología Industrial , Ácido Cítrico/metabolismo , FermentaciónRESUMEN
Xanthan gum is a microbial polysaccharide produced by Xanthomonas and widely used in various industries. To produce xanthan gum, the native Xanthomonas citri-386 was used in a cheese-whey-based culture medium. The culture conditions were investigated in batch experiments based on the response surface methodology to increase xanthan production and viscosity. Three independent variables in this study included feeding times of acetate, pyruvate, and citrate. The maximum xanthan gum production and viscosity within 120 h by X. citri-386 using Box-Behnken design were 25.7 g/l and 65 500 cP, respectively, with a 151% and 394% increase as compared to the control sample. Overall, the findings of this study recommend the use of X. citri-386 in the cheese-whey-based medium as an economical medium with optimal amounts of acetate, pyruvate, and citrate for commercial production of xanthan gum on an industrial scale. The adjustment of the pyruvate and acetate concentrations optimized xanthan gum production in the environment.
Asunto(s)
Acetatos , Ácido Cítrico , Medios de Cultivo , Polisacáridos Bacterianos , Ácido Pirúvico , Xanthomonas , Polisacáridos Bacterianos/biosíntesis , Polisacáridos Bacterianos/metabolismo , Xanthomonas/metabolismo , Xanthomonas/crecimiento & desarrollo , Ácido Pirúvico/metabolismo , Ácido Cítrico/metabolismo , Medios de Cultivo/química , Acetatos/metabolismo , ViscosidadRESUMEN
The prevailing biomarker employed for prostate cancer (PCa) screening and diagnosis is the prostate-specific antigen (PSA). Despite excellent sensitivity, PSA lacks specificity, leading to false positives, unnecessary biopsies and overdiagnosis. Consequently, PSA is increasingly less used by clinicians, thus underscoring the imperative for the identification of new biomarkers. An emerging biomarker in this context is citrate, a molecule secreted by the normal prostate, which has been shown to be inversely correlated with PCa. Here, we discuss about PSA and its usage for PCa diagnosis, its lack of specificity, and the various conditions that can affect its levels. We then provide our vision about what we think would be a valuable addition to our PCa diagnosis toolkit, citrate. We describe the unique citrate metabolic program in the prostate and how this profile is reprogrammed during carcinogenesis. Finally, we summarize the evidence that supports the usage of citrate as a biomarker for PCa diagnosis, as it can be measured in various patient samples and be analyzed by several methods. The unique relationship between citrate and PCa, combined with the stability of citrate levels in other prostate-related conditions and the simplicity of its detection, further accentuates its potential as a biomarker.
Asunto(s)
Biomarcadores de Tumor , Ácido Cítrico , Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/metabolismo , Antígeno Prostático Específico/sangre , Biomarcadores de Tumor/sangre , Ácido Cítrico/metabolismo , Próstata/patología , Próstata/metabolismoRESUMEN
Citrate synthase catalyzes the first and the rate-limiting reaction of the tricarboxylic acid (TCA) cycle, producing citrate from the condensation of oxaloacetate and acetyl-coenzyme A. The parasitic protozoan Toxoplasma gondii has full TCA cycle activity, but its physiological roles remain poorly understood. In this study, we identified three proteins with predicted citrate synthase (CS) activities two of which were localized in the mitochondrion, including the 2-methylcitrate synthase (PrpC) that was thought to be involved in the 2-methylcitrate cycle, an alternative pathway for propionyl-CoA detoxification. Further analyses of the two mitochondrial enzymes showed that both had citrate synthase activity, but the catalytic efficiency of CS1 was much higher than that of PrpC. Consistently, the deletion of CS1 resulted in a significantly reduced flux of glucose-derived carbons into TCA cycle intermediates, leading to decreased parasite growth. In contrast, disruption of PrpC had little effect. On the other hand, simultaneous disruption of both CS1 and PrpC resulted in more severe metabolic changes and growth defects than a single deletion of either gene, suggesting that PrpC does contribute to citrate production under physiological conditions. Interestingly, deleting Δcs1 and Δprpc individually or in combination only mildly or negligibly affected the virulence of parasites in mice, suggesting that both enzymes are dispensable in vivo. The dispensability of CS1 and PrpC suggests that either the TCA cycle is not essential for the asexual reproduction of tachyzoites or there are other routes of citrate supply in the parasite mitochondrion.
Asunto(s)
Citrato (si)-Sintasa , Ciclo del Ácido Cítrico , Ácido Cítrico , Mitocondrias , Proteínas Protozoarias , Toxoplasma , Toxoplasma/enzimología , Toxoplasma/metabolismo , Toxoplasma/genética , Mitocondrias/metabolismo , Animales , Citrato (si)-Sintasa/metabolismo , Citrato (si)-Sintasa/genética , Ácido Cítrico/metabolismo , Ratones , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/genética , Toxoplasmosis/metabolismo , Toxoplasmosis/parasitología , Toxoplasmosis/genéticaRESUMEN
The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.
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Ácido Cítrico , Dieta Alta en Grasa , Pez Cebra , Animales , Dieta Alta en Grasa/efectos adversos , Ácido Cítrico/metabolismo , Síndrome Metabólico/metabolismo , Síndrome Metabólico/prevención & control , Síndrome Metabólico/genética , Síndrome Metabólico/etiología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Obesidad/metabolismo , Obesidad/prevención & control , Obesidad/genética , Obesidad/etiología , Acetilación , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Resistencia a la Insulina , Hígado Graso/metabolismo , Hígado Graso/prevención & control , Hígado Graso/patología , Hígado Graso/etiología , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.
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Benzo(a)pireno , Biodegradación Ambiental , Ácido Cítrico , Contaminantes del Suelo , Benzo(a)pireno/toxicidad , Benzo(a)pireno/metabolismo , Ácido Cítrico/metabolismo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Lacasa/metabolismo , Microbiología del Suelo , Polyporaceae/metabolismo , Trametes/metabolismo , BiomasaRESUMEN
Pathogenic bacteria's metabolic adaptation for survival and proliferation within hosts is a crucial aspect of bacterial pathogenesis. Here, we demonstrate that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, plays a key role as a regulator of gene expression in Staphylococcus aureus. We show that citrate activates the transcriptional regulator CcpE and thus modulates the expression of numerous genes involved in key cellular pathways such as central carbon metabolism, iron uptake and the synthesis and export of virulence factors. Citrate can also suppress the transcriptional regulatory activity of ferric uptake regulator. Moreover, we determined that accumulated intracellular citrate, partly through the activation of CcpE, decreases the pathogenic potential of S. aureus in animal infection models. Therefore, citrate plays a pivotal role in coordinating carbon metabolism, iron homeostasis, and bacterial pathogenicity at the transcriptional level in S. aureus, going beyond its established role as a TCA cycle intermediate.
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Carbono , Ácido Cítrico , Regulación Bacteriana de la Expresión Génica , Homeostasis , Hierro , Infecciones Estafilocócicas , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Hierro/metabolismo , Carbono/metabolismo , Ácido Cítrico/metabolismo , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Animales , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Ciclo del Ácido Cítrico , Ratones , Transducción de SeñalRESUMEN
Excessive heavy metal contaminants in soils have serious ecological and environmental impacts, and affect plant growth and crop yields. Phytoremediation is an environmentally friendly means of lowering heavy metal concentrations in soils. In this study, we analyzed phenotypic and physiological traits, and the transcriptome and metabolome, of sheepgrass (Leymus chinensis) exposed to cadmium (Cd), lead (Pb), or zinc (Zn). Phenotypic and physiological analysis indicated that sheepgrass had strong tolerance to Cd/Pb/Zn. Transcriptomic analysis revealed that phenylpropanoid biosynthesis and organic acid metabolism were enriched among differentially expressed genes, and metabolomic analysis indicated that the citrate cycle was enriched in response to Cd/Pb/Zn exposure. Genes encoding enzymes involved in the phenylpropanoid and citrate cycle pathways were up-regulated under the Cd/Pb/Zn treatments. Organic acids significantly reduced heavy metal accumulation and improved sheepgrass tolerance of heavy metals. The results suggest that synergistic interaction of the phenylpropanoid and citrate cycle pathways in sheepgrass roots induced organic acid secretion to alleviate heavy metal toxicity. A cascade of enzymes involved in the interacting pathways could be targeted in molecular design breeding to enhance phytoremediation.
Asunto(s)
Biodegradación Ambiental , Metales Pesados , Contaminantes del Suelo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Metales Pesados/metabolismo , Metales Pesados/toxicidad , Cadmio/toxicidad , Cadmio/metabolismo , Poaceae/metabolismo , Poaceae/efectos de los fármacos , Ciclo del Ácido Cítrico/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Zinc/metabolismo , Plomo/toxicidad , Plomo/metabolismo , Transcriptoma/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ácido Cítrico/metabolismoRESUMEN
The senescent microenvironment and aged cells per se contribute to tissue remodeling, chronic inflammation, and age-associated dysfunction. However, the metabolic and epigenomic bases of the senescence-associated secretory phenotype (SASP) remain largely unknown. Here, we show that ATP-citrate lyase (ACLY), a key enzyme in acetyl-coenzyme A (CoA) synthesis, is essential for the pro-inflammatory SASP, independent of persistent growth arrest in senescent cells. Citrate-derived acetyl-CoA facilitates the action of SASP gene enhancers. ACLY-dependent de novo enhancers augment the recruitment of the chromatin reader BRD4, which causes SASP activation. Consistently, specific inhibitions of the ACLY-BRD4 axis suppress the STAT1-mediated interferon response, creating the pro-inflammatory microenvironment in senescent cells and tissues. Our results demonstrate that ACLY-dependent citrate metabolism represents a selective target for controlling SASP designed to promote healthy aging.
Asunto(s)
ATP Citrato (pro-S)-Liasa , Senescencia Celular , Ácido Cítrico , Factores de Transcripción , Animales , Humanos , ATP Citrato (pro-S)-Liasa/metabolismo , ATP Citrato (pro-S)-Liasa/genética , Ácido Cítrico/metabolismo , Factores de Transcripción/metabolismo , Ratones , Inflamación/metabolismo , Inflamación/patología , Microambiente Celular , Acetilcoenzima A/metabolismo , Elementos de Facilitación Genéticos/genética , Ratones Endogámicos C57BL , Proteínas Nucleares/metabolismoRESUMEN
The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.
Asunto(s)
Cíclidos , Ácido Cítrico , Metabolismo de los Lípidos , Hígado , Triglicéridos , Animales , Triglicéridos/metabolismo , Hígado/metabolismo , Masculino , Cíclidos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Ácido Cítrico/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Proteínas de Peces/metabolismo , Acetilcoenzima A/metabolismoRESUMEN
In acidic soils, aluminum (Al) toxicity inhibits the growth and development of plant roots and affects nutrient and water absorption, leading to reduced yield and quality. Therefore, it is crucial to investigate and identify candidate genes for Al tolerance and elucidate their physiological and molecular mechanisms under Al stress. In this study, we identified a new gene OsAlR3 regulating Al tolerance, and analyzed its mechanism from physiological, transcriptional and metabolic levels. Compared with the WT, malondialdehyde (MDA) and hydrogen peroxide (H2O2) content were significantly increased, superoxide dismutase (SOD) activity and citric acid (CA) content were significantly decreased in the osalr3 mutant lines when exposed to Al stress. Under Al stress, the osalr3 exhibited decreased expression of antioxidant-related genes and lower organic acid content compared with WT. Integrated transcriptome and metabolome analysis showed the phenylpropanoid biosynthetic pathway plays an important role in OsAlR3-mediated Al tolerance. Exogenous CA and oxalic acid (OA) could increase total root length and enhance the antioxidant capacity in the mutant lines under Al stress. Conclusively, we found a new gene OsAlR3 that positively regulates Al tolerance by promoting the chelation of Al ions through the secretion of organic acids, and increasing the expression of antioxidant genes.