Iron sensing metabolic pathway

Heme biosynthesis in the Gram-positive bacteria occurs mostly via a pathway that is distinct from that of eukaryotes and Gram-negative bacteria in the three terminal heme synthesis steps. In many of these bacteria heme is a necessary cofactor that fulfills roles in respiration, gas sensing, and detoxification of reactive oxygen species. These varying roles for heme, the requirement of iron and glutamate, as glutamyl tRNA, for synthesis, and the sharing of intermediates with the synthesis of other porphyrin derivatives necessitates the need for many points of regulation in response to nutrient availability and metabolic state...

Plant growth relies on the mineral nutrients present in the rhizosphere. The distribution of nutrients in soils varies depending on their mobility and capacity to bind with soil particles. Consequently, plants often encounter either low or high levels of nutrients in the rhizosphere. Plant roots are the essential organs that sense changes in soil mineral content, leading to the activation of signaling pathways associated with the adjustment of plant architecture and metabolic responses. During differential availability of minerals in the rhizosphere, plants trigger adaptation strategies such as cellular remobilization of minerals, secretion of organic molecules, and the attenuation or enhancement of root growth to balance nutrient uptake...

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them...

BACKGROUND: Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered tumor metabolism favoring aerobic glycolysis, a phenomenon known as the Warburg effect...

Nanoparticle-based formulations are considered valuable tools for diagnostic and treatment purposes. The surface decoration of nanoparticles with polyethyleneimine (PEI) is often used to enhance their targeting and functional properties. Here, we aimed at addressing the long-term fate in vivo and the potential "off-target" effects of PEI decorated iron oxide nanoparticles (PEI-MNPs) in individuals with low-grade and persistent systemic inflammation. For this purpose, we synthesized PEI-MNPs (core-shell method, PEI coating under high pressure homogenization)...

The quorum sensing two-component system (TCS) QseBC has been linked to virulence, motility and metabolism regulation in multiple Gram-negative pathogens, including Enterohaemorrhagic Escherichia coli (EHEC), Uropathogenic E. coli (UPEC) and Salmonella enterica. In EHEC, the sensor histidine kinase (HK) QseC detects the quorum sensing signalling molecule AI-3 and also acts as an adrenergic sensor binding host epinephrine and norepinephrine. Downstream changes in gene expression are mediated by phosphorylation of its cognate response regulator (RR) QseB, and 'cross-talks' with non-cognate regulators KdpE and QseF to activate motility and virulence...

Here, we investigate the transcriptome profiles of two S. Enteritidis and one S. Schwarzengrund isolates that present different persister levels when exposed to ciprofloxacin or ceftazidime. It was possible to note a distinct transcript profile among isolates, time of exposure, and treatment. We could not find a commonly expressed transcript profile that plays a role in persister formation after S. enterica exposure to beta-lactam or fluoroquinolone, as only three DEGs presented the same behavior under the conditions and isolates tested...

Microbial communication can drive coordinated functions through sensing, analyzing and processing signal information, playing critical roles in biomanufacturing and life evolution. However, it is still a great challenge to develop effective methods to construct a microbial communication system with coordinated behaviors. Here, we report an electron transfer triggered redox communication network consisting of three building blocks including signal router, optical verifier and bio-actuator for microbial metabolism regulation and coordination...

The human mitochondrial ribosome contains three [2Fe-2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the expression of Fe-S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [2Fe-2S] clusters from the GLRX5-BOLA3 node...

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values...

All eukaryotic cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here we report a previously undescribed eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter, LAT3, and RPTOR...

Ferroptosis is a non-apoptotic cell death regulated by iron-dependent lipid peroxidation. Glutathione (GSH), a key antioxidant against oxidative damage, is involved in one of the most important metabolic pathways of ferroptosis. Herein, an excellent plasmonic nanoprobe was developed for highly sensitive, in situ, dynamic real-time monitoring of intracellular GSH levels during ferroptosis. A nanoprobe was prepared by functionalizing gold nanoparticles (AuNPs) with the probe molecule crystal violet (CV). The fluctuation in the SERS signal intensity of CV via the competitive displacement reaction can be used to detect GSH...

The perception of sepsis has shifted over time; however, it remains a leading cause of death worldwide. Sepsis is now recognized as an imbalance in host cellular functions triggered by the invading pathogens, both related to immune cells, endothelial function, glucose and oxygen metabolism, tissue repair and restoration. Many of these key mechanisms in sepsis are also targets of hyperbaric oxygen (HBO2 ) treatment. HBO2 treatment has been shown to improve survival in clinical studies on patients with necrotizing soft tissue infections as well as experimental sepsis models...

Iron sulfur clusters (ISC) are essential cofactors that participate in electron transfer, environmental sensing, and catalysis. Amongst the most ancient ISC containing proteins are the ferredoxin family of electron carriers. Humans have two ferredoxins, FDX1 and FDX2, both of which are localized to mitochondria, and the latter of which is itself important for ISC synthesis. We have previously shown that hypoxia can eliminate the requirement for some components of the ISC biosynthetic pathway, but ferredoxins were not included in that study...

BACKGROUND: Adaptation to complex, rapidly changing environments is crucial for evolutionary success of fungi. The heterotrimeric G-protein pathway belongs to the most important signaling cascades applied for this task. In Trichoderma reesei, enzyme production, growth and secondary metabolism are among the physiological traits influenced by the G-protein pathway in a light dependent manner. RESULTS: Here, we investigated the function of the SNX/H-type regulator of G-protein signaling (RGS) protein RGS4 of T...

Microbes utilize numerous metal cofactor-containing proteins to recognize and respond to constantly fluctuating redox stresses in their environment. Gaining an understanding of how these metalloproteins sense redox events, and how they communicate such information downstream to DNA to modulate microbial metabolism, is a topic of great interest to both chemists and biologists. In this article, we review recently characterized examples of metalloprotein sensors, focusing on the coordination and oxidation state of the metals involved, how these metals are able to recognize redox stimuli, and how the signal is transmitted beyond the metal center...

Pseudomonads are metabolically flexible and can thrive on different plant hosts. However, the metabolic adaptations required for host promiscuity are unknown. Here, we addressed this knowledge gap by employing RNAseq and comparing transcriptomic responses of Pseudomonas donghuensis P482 to root exudates of two plant hosts: tomato and maize. Our main goal was to identify the differences and the common points between these two responses. Pathways upregulated only by tomato exudates included nitric oxide detoxification, repair of iron-sulfur clusters, respiration through the cyanide-insensitive cytochrome bd, and catabolism of amino and/or fatty acids...

Congenital erythrocytoses represent a heterogenous group of rare defects of erythropoiesis characterized by elevated erythrocyte mass. We performed molecular-genetic analysis of 21 Czech patients with congenital erythrocytosis and assessed the mutual link between chronic erythrocyte overproduction and iron homoeostasis. Causative mutations in erythropoietin receptor (EPOR), hypoxia-inducible factor 2 alpha (HIF2A) or Von Hippel-Lindau (VHL) genes were detected in nine patients, including a novel p.A421Cfs*4 EPOR and a homozygous intronic c...

To ensure proper utilization of iron and avoid its toxicity, cells are equipped with iron-sensing proteins to maintain cellular iron homeostasis. We showed previously that NCOA4, a ferritin-specific autophagy adapter, intricately regulates the fate of ferritin; upon binding to Fe3+ , NCOA4 forms insoluble condensates and regulates ferritin autophagy in iron-replete conditions. Here, we demonstrate an additional iron-sensing mechanism of NCOA4. Our results indicate that the insertion of an Fe-S cluster enables preferential recognition of NCOA4 by the HERC2 ubiquitin ligase in iron-replete conditions, resulting in degradation by the proteasome and subsequent inhibition of ferritinophagy...

Over the past few decades, a close relationship between sulfur (S) and iron (Fe) in terms of functionality and nutrition was demonstrated in the tomato. However, very little is known about the regulatory mechanisms underlying S/Fe interactions. Recently, the potential role of citrate in plant adaptation to Fe deficiency and combined S and Fe deficiency has been described. It is known that an impaired organic acid metabolism may stimulate a retrograde signal, which has been proven to be linked to the Target of Rapamycin (TOR) signaling in yeast and animal cells...