Disruption of Iron Homeostasis Sensitizes Pancreatic Cancer to Irreversible Electroporation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Jun Zhao
PROVIDER: PXD063472 | iProX | Wed Apr 30 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Iron–sulfur (Fe–S) clusters play an essential role in plants as protein cofactors mediating diverse electron transfer reactions. Because they can react with oxygen to form reactive oxygen species (ROS) and inflict cellular damage, the biogenesis of Fe–S clusters is highly regulated. A recently discovered group of 2Fe–2S proteins, termed NEET proteins, was proposed to coordinate Fe–S, Fe and ROS homeostasis in mammalian cells. Here we report that disrupting the function of AtNEET, the sole member of the NEET protein family in Arabidopsis thaliana, triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses, elevated Fe content in chloroplasts (1.2–1.5‐fold), chlorosis, structural damage to chloroplasts and a high seedling mortality rate. Our findings suggest that disrupting AtNEET function disrupts the transfer of 2Fe–2S clusters from the chloroplastic 2Fe–2S biogenesis pathway to different cytosolic and chloroplastic Fe–S proteins, as well as to the cytosolic Fe–S biogenesis system, and that uncoupling this process triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses that result in Fe over‐accumulation in chloroplasts and enhanced ROS accumulation. We further show that AtNEET transfers its 2Fe–2S clusters to DRE2, a key protein of the cytosolic Fe–S biogenesis system, and propose that the availability of 2Fe–2S clusters in the chloroplast and cytosol is linked to Fe homeostasis in plants.
2019-12-22 | GSE127300 | GEO
Project description:Iron (Fe) is an essential micronutrient for the survival and proliferation of plants. Plants have evolved complex mechanisms to maintain Fe homeostasis in response of Fe deficiency conditions. To explore the mechanisms of Populus tomentosa response to Fe deficiency, we evaluated the physiological, biochemical and transcriptome differences of P. tomentosa between Fe-sufficient and Fe-deficient conditions. The results showed that, under Fe-free conditions, the chlorophyll synthesis and photosynthesis pathways in shoots were extremely depressed. The inhibition of these pathways caused chlorosis and reduced shoot growth. Meanwhile, although both two photosynthetic systems (PSI and PSII) were inhibited under Fe limited conditions, PSI is affected more serious and earlier than PSII. In order to maintain Fe homeostasis, several genes involved in Fe regulation network were differentially expressed. At the late period of Fe deficiency response, some genes (BTS, bHLH38/39 and PYE) in PYE regulatory network were up-regulated in roots, while some root-specific ethylene-dependent FIT regulatory genes (EIN3, ERF and FIT) were down-regulated. Moreover, FRO2 was induced in P. tomentosa roots to reduce more Fe3+, which is similar with other strategy I plants. It is interest that we found another Fe2+ transporter gene (NRAMP1) was induced, instead of the well-known Fe2+ transporter gene (IRT1) for strategy I plants, to promote Fe2+ absorption at the Fe deficiency late stage.
2020-01-01 | GSE116838 | GEO
Project description:Iron and manganese are part of a small group of transition metals required for photosynthetic electron transport. Here, we present evidence for a functional link between iron and manganese homeostasis. In the unicellular cyanobacterium, Synechocystis sp. PCC 6803 Fe and Mn deprivation resulted in distinct modifications of the function of the photosynthetic apparatus. For example, iron limitation modifies the rate of QA re-oxidation in photosystem II, a complex that contains more Mn than Fe. The intracellular elemental quotas of Fe and Mn are also linked. Fe limitation reduces the intracellular Mn quota. Mn limitation did not exert a reciprocal effect on Fe quotas. Microarray analysis comparing Mn and Fe limitation revealed a stark difference in the extent of the transcriptional response to the two limiting conditions, reflective of the physiological data. The effects of Fe limitation on the transcriptional network are widespread while the effects on Mn limitation are highly specific. Our analysis also revealed an overlap in the transcriptional response of specific Fe and Mn transporters. This overlap provides a framework for explaining Fe limitation induced changes in Mn quotas. Fe transporters can serve as a low affinity Mn transport system. Under iron limitation the specificity of the Fe transport system changes, making it a less efficient Mn transport system.
2013-06-29 | GSE48416 | GEO
Project description:To control infection, mammals actively withhold essential nutrients, including the transition metal manganese, by a process termed nutritional immunity. A critical component of this host response is the manganese-chelating protein calprotectin. While many bacterial mechanisms for overcoming nutritional immunity have been identified, the intersection between metal starvation and other essential inorganic nutrients has not been investigated. Here, we report that overexpression of an operon encoding a highly conserved inorganic phosphate importer, PstSCAB, increases the sensitivity of Staphylococcus aureus to calprotectin-mediated manganese sequestration. Further analysis revealed that overexpression of pstSCAB does not disrupt manganese acquisition or result in overaccumulation of phosphate by S. aureus However, it does reduce the ability of S. aureus to grow in phosphate-replete defined medium. Overexpression of pstSCAB does not aberrantly activate the phosphate-responsive two-component system PhoPR, nor was this two-component system required for sensitivity to manganese starvation. In a mouse model of systemic staphylococcal disease, a pstSCAB-overexpressing strain is significantly attenuated compared to wild-type S. aureus This defect is partially reversed in a calprotectin-deficient mouse, in which manganese is more readily available. Given that expression of pstSCAB is regulated by PhoPR, these findings suggest that overactivation of PhoPR would diminish the ability of S. aureus to resist nutritional immunity and cause infection. As PhoPR is also necessary for bacterial virulence, these findings imply that phosphate homeostasis represents a critical regulatory node whose activity must be precisely controlled in order for S. aureus and other pathogens to cause infection.
| S-EPMC7240092 | biostudies-literature
Project description:Iron and manganese are part of a small group of transition metals required for photosynthetic electron transport. Here, we present evidence for a functional link between iron and manganese homeostasis. In the unicellular cyanobacterium, Synechocystis sp. PCC 6803 Fe and Mn deprivation resulted in distinct modifications of the function of the photosynthetic apparatus. For example, iron limitation modifies the rate of QA re-oxidation in photosystem II, a complex that contains more Mn than Fe. The intracellular elemental quotas of Fe and Mn are also linked. Fe limitation reduces the intracellular Mn quota. Mn limitation did not exert a reciprocal effect on Fe quotas. Microarray analysis comparing Mn and Fe limitation revealed a stark difference in the extent of the transcriptional response to the two limiting conditions, reflective of the physiological data. The effects of Fe limitation on the transcriptional network are widespread while the effects on Mn limitation are highly specific. Our analysis also revealed an overlap in the transcriptional response of specific Fe and Mn transporters. This overlap provides a framework for explaining Fe limitation induced changes in Mn quotas. Fe transporters can serve as a low affinity Mn transport system. Under iron limitation the specificity of the Fe transport system changes, making it a less efficient Mn transport system. We monitored the gene expression of Synechocystis PCC6083 at standard conditions and after 2 days of iron limitation (0Fe), manganese limitation (0Mn) and combined iron and manganese limitation (0Fe0Mn). Each timepoint and condition was sampled in triplicates. Due to strong deviations in one of the three repeats for the 0Mn and 0Fe0Mn conditions, the corresponding replicates were excluded from further analysis.
2013-06-29 | E-GEOD-48416 | biostudies-arrayexpress
Project description:NADPH-dependent thioredoxin reductase C (NTRC) plays a central role in redox regulation of chloroplast photosynthetic metabolism. Accordingly, Arabidopsis (Arabidopsis thaliana) NTRC null mutants show defective photosynthetic performance and growth inhibition. Remarkably, these mutants show almost wild type phenotype at the seedling stage, which raises the question of whether NTRC plays different functions throughout plant development. In this work, we have addressed this issue by performing transcriptome comparisons of Arabidopsis wild type and ntrc mutant lines at seedling and adult stages of development. In contrast with the high impact of NTRC on leaves from adult plants, the low transcriptomic differences in seedlings suggested a less-relevant function of NTRC at this stage of plant development. Notably, the ntrc mutant showed transcriptomic changes resembling the response to Fe excess throughout plant development, though this response was almost unique at the seedling stage. The lack of NTRC caused altered levels of Mn, Zn, Cu, S, P, K and Na, but no significant differences in the content of Fe, as compared with the wild type. Moreover, at the seedling stage, the lack of NTRC caused hypersensitivity to Fe deficit, but a protective effect in response to Fe excess, most likely due to lower ROS accumulation in the mutant seedlings. Our results reveal the different impact of NTRC throughout plant development and identify Fe homeostasis as a process highly affected by NTRC, most notably at the seedling stage.
2025-04-11 | GSE285082 | GEO
Project description:Transcriptional profiling of rice genes analyzing the effect of knockdown of OsHRZ1 and OsHRZ2 in HRZ2i lines. NT and HRZ2i lines 1, 2 and 3 (2i-1, 2i-2 and 2i-3, respectively) were treated under iron sufficiency for 7 days (+Fe 7d) or under iron deficiency for 1 day (-Fe 1d) or 7 days (-Fe 7d) in hydroponic culture.
2013-10-17 | GSE39906 | GEO
Project description:<p>High-affinity iron (Fe) scavenging compounds, or siderophores, are widely employed by soil bacteria to survive scarcity in bioavailable Fe. Siderophore biosynthesis relies on cellular carbon metabolism, despite reported decrease in both carbon uptake and Fe-containing metabolic proteins in Fe-deficient cells. Given this paradox, the metabolic network required to sustain the Fe-scavenging strategy is poorly understood. Here, through multiple <sup>13</sup>C-metabolomics experiments with Fe-replete and Fe-limited cells, we uncover how soil <em>Pseudomonas</em> species reprogram their metabolic pathways to prioritize siderophore biosynthesis. Across the three species investigated (<em>Pseudomonas putida</em> KT2440, <em>Pseudomonas protegens</em> Pf-5, and <em>Pseudomonas putida</em> S12), siderophore secretion is higher during growth on gluconeogenic substrates than during growth on glycolytic substrates. In response to Fe limitation, we capture decreased flux toward the tricarboxylic acid (TCA) cycle during the metabolism of glycolytic substrates but, due to carbon recycling to the TCA cycle via enhanced anaplerosis, the metabolism of gluconeogenic substrates results in an increase in both siderophore secretion (up to threefold) and Fe extraction (up to sixfold) from soil minerals. During simultaneous feeding on the different substrate types, Fe deficiency triggers a hierarchy in substrate utilization, which is facilitated by changes in protein abundances for substrate uptake and initial catabolism. Rerouted metabolism further promotes favorable fluxes in the TCA cycle and the gluconeogenesis-anaplerosis nodes, despite decrease in several proteins in these pathways, to meet carbon and energy demands for siderophore precursors in accordance with increased proteins for siderophore biosynthesis. Hierarchical carbon metabolism thus serves as a critical survival strategy during the metal nutrient deficiency.</p><p><br></p><p><strong>Data availability:</strong></p><p>The proteomics data have been deposited into the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier <a href='https://www.ebi.ac.uk/pride/archive/projects/PXD013605' rel='noopener noreferrer' target='_blank'>PXD013605</a>.</p>
2020-12-05 | MTBLS1715 | MetaboLights
Project description:Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.
| S-EPMC6446870 | biostudies-literature
Project description:The antagonistic interaction between iron (Fe) and phosphorus (P) has been noted in the area of plant nutrition. To understand the physiology and molecular mechanisms of this interaction, we studied the growth performance, nutrient concentration, and gene expression profiles of root and shoot segments derived from 10-d-old rice (Oryza sativa) seedlings under four different nutrient conditions: (1) full strength of Fe and P (+Fe+P); (2) full strength of P and no Fe (-Fe+P); (3) full strength of Fe and no P (+Fe-P); and (4) without both Fe and P (-Fe-P). We used Affymetrix genechip to detail the global programme of gene expression underlying different Fe and P supply conditions identified distinct classes of up-regulated genes.
2009-07-22 | GSE17245 | GEO