Metallomics最新文献

{"title":"Association of metal elements deposition with symptomatic carotid artery stenosis and their spatial distribution in atherosclerosis plaques.","authors":"Liangran Huang, Yacong Liu, Lebao Yu, Aichun Cheng, Jingli Cao, Rong Wang, Yue Liu, Shuang Song, Wei Zhao, Qian Liu, Dong Zhang","doi":"10.1093/mtomcs/mfaf019","DOIUrl":"10.1093/mtomcs/mfaf019","url":null,"abstract":"<p><p>Metals in circulation and urine had been implicated in atherosclerosis progression, but spatial distribution of metals within plaques and their association with plaque stability remained unclear. This study aimed to clarify differences of metal deposition between symptomatic and asymptomatic carotid plaques and metal spatial distribution within atherosclerotic plaques. We enrolled 15 asymptomatic and 53 symptomatic atherosclerotic plaque specimens during carotid endarterectomy. Each plaque was divided into the plaque core and thickened intimal area. We analyzed the difference of metals within plaques between symptomatic and asymptomatic groups and correlations between age and metal deposition. Besides, 12 additional symptomatic atherosclerotic plaques were used to map metal element distribution by laser ablation inductively coupled plasma mass spectrometry to analyze relative abundance of metal across pathological characteristics of plaques. Significantly higher levels of vanadium, iron, copper, molybdenum, and cadmium were found in the core area of symptomatic plaques compared to asymptomatic plaques, while no difference was observed in plaque thickened intimal area. Copper and lead deposition in core region of symptomatic plaques significantly increased with age. Spatial mapping indicated distinct metal distribution patterns: copper was primarily localized in necrotic and calcified regions, iron was in intraplaque hemorrhage, and calcium and zinc were in calcified areas. Elevated metal accumulation and distinct spatial distribution of metal elements within atherosclerotic plaques might contribute to plaque instability. Our findings highlighted the potential role of metal elements in plaque progression and value of spatial localization methods in studying the pathological roles of metal elements.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rust and redemption: iron-sulfur clusters and oxygen in human disease and health.","authors":"Shany Egozi, Tslil Ast","doi":"10.1093/mtomcs/mfaf022","DOIUrl":"10.1093/mtomcs/mfaf022","url":null,"abstract":"<p><p>Iron-sulfur (Fe-S) clusters are ancient and versatile cofactors that drive essential cellular functions, from electron transport to enzyme catalysis. Their intrinsic sensitivity to oxidation has shaped the evolution of specialized Fe-S cluster biosynthetic and protective mechanisms. Recent findings highlight how human Fe-S-binding regulators exploit this cofactor's reactivity to sense iron and oxygen levels, translating environmental cues into appropriate homeostatic responses. Yet, the same redox sensitivity also renders Fe-S cluster proteins and biosynthesis particularly vulnerable to high oxygen tensions, contributing to pathological outcomes. In this minireview, we examine key discoveries illustrating how Fe-S clusters and oxygen intersect to influence both human health and disease. Finally, we discuss how identifying novel Fe-S targets and regulatory circuits may open innovative therapeutic avenues-harnessing oxygen itself as a strategic element in managing relevant disorders.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Iron Metalloproteome of Pseudomonas aeruginosa Under Oxic, Anoxic Conditions.","authors":"Mak Saito, Matthew R McIlvin","doi":"10.1093/mtomcs/mfaf023","DOIUrl":"10.1093/mtomcs/mfaf023","url":null,"abstract":"<p><p>Pseudomonas aeruginosa is a major contributor to human infections and is widely distributed in the environment. Its ability for growth under aerobic and anaerobic conditions provides adaptability to environmental changes and in confronting immune responses. We applied native 2-dimensional metalloproteomics to P. aeruginosa to examine how use of iron within the metallome responds to oxic and anoxic conditions. Analyses revealed four iron peaks comprised of metalloproteins with synergistic functions, including: 1) respiratory and metabolic enzymes, 2) oxidative stress response enzymes, 3) DNA synthesis and nitrogen assimilation enzymes, and 4) denitrification enzymes and related copper enzymes. Fe peaks were larger under anoxic conditions, consistent with increased iron demand due to anaerobic metabolism and with the denitrification peak absent under oxic conditions. Three ferritins co-eluted with the first and third iron peaks, localizing iron storage with these functions. Several enzymes were more abundant at low oxygen, including alkylhydroperoxide reductase C that deactivates organic radicals produced by denitrification, all three classes of ribonucleotide reductases (including monomers and oligomer forms), ferritin (increasing in ratio relative to bacterioferritin), and denitrification enzymes. Superoxide dismutase and homogentisate 1,2-dioxygenase were more abundant at high oxygen. Several Fe peaks contained iron metalloproteins that co-eluted earlier than their predicted size, implying additional protein-protein interactions and suggestive of cellular organization that contributes to iron prioritization in Pseudomonas with its large genome and flexible metabolism. This study characterized the iron metalloproteome of one of the more complex prokaryotic microorganisms, attributing enhanced iron use under anaerobic denitrifying metabolism to its specific metalloprotein constituents. The iron metalloproteome of Pseudomonas aeruginosa was examined using native (non-denaturing) 2-dimensional chromatographic separation coupled to elemental and proteomic mass spectrometries. (A) Four major iron peaks were observed that corresponded to multi-protein complexes associated with respiratory, (B) antioxidant, DNA production, and denitrification functions, and associated iron storage and supply. The results suggest the presence of protein assemblies with potential roles in iron homeostasis and trafficking.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies and Tactics for Subcellular Targeting of Small Molecule Zinc Sensors.","authors":"William K McCarthy, Jason M Mrosla, Brian Pallares, Jacob M Goldberg","doi":"10.1093/mtomcs/mfaf024","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf024","url":null,"abstract":"<p><p>Zinc(II) ions play manifold roles in human health; dysregulation of zinc homeostasis has been implicated in a number of diseases and pathological conditions. Because zinc(II) is spectroscopically silent, it cannot be detected directly by conventional fluorescence microscopy. As a result, investigators seeking to image zinc(II) in biological systems frequently turn to small-molecule fluorescent sensors that selectively respond to the presence of the ion. This tutorial review describes methods for delivering such small-molecule probes to discrete subcellular locales. Attention is given to the preparation of conjugates in which well-characterized sensors are tethered to molecular homing moieties that accumulate in particular organelles or other compartments. Hybrid approaches that entail enzyme-mediated localization of synthetic constructs, as well as other novel techniques, are also discussed. The various fluorescent probe targeting methods described here enable opportunities for new discoveries in zinc biology.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons.","authors":"Aiyarin Kittilukkana, Asuncion Carmona, Léa Normand, Coline Gibout, Andrea Somogyi, Chalermchai Pilapong, Richard Ortega","doi":"10.1093/mtomcs/mfaf021","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf021","url":null,"abstract":"<p><p>Iron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated in neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular iron, plays a prominent role in iron-induced neurological damage. However, the mechanisms governing the detoxification and transport of labile iron within neurons are not fully understood. This study investigates the storage and transport of labile ferrous iron Fe(II) in cultured primary rat hippocampal neurons. Iron distribution was studied using live cell fluorescence microscopy with a selective labile Fe(II) fluorescent dye, and synchrotron X-ray fluorescence microscopy (SXRF) for total iron distribution. Fluorescent labelling of the axon initial segment and of lysosomes allowed iron distribution to be correlated with these subcellular compartments. The results show that labile Fe(II) is stored in lysosomes within somas, axons and dendrites and that lysosomal labile Fe(II) is transported retrogradely and anterogradely along axons and dendrites. In addition, SXRF imaging of total iron confirms iron uptake and iron distribution in the form of iron-rich dots in the soma and neurites. These results suggest that after exposure to Fe(II), labile Fe(II) is stored in lysosomes and can be transported along dendrites and axons. These storage and transport mechanisms could be associated with the detoxification of reactive Fe(II) in lysosomes, which protects cellular structures from oxidative stress. They could also be associated with the metabolic functions of iron in the soma, axons and dendrites. In this case, easily exchangeable Fe(II) is transported in lysosomes to the neuronal compartments where iron is required.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of zinc homeostasis mechanisms in Pseudomonas aeruginosa through data-dependent and data-independent acquisition mass spectrometry.","authors":"Annaliese C S Meyer, Matthew R McIlvin, Paloma Zaria Lopez, Brian C Searle, Mak Saito","doi":"10.1093/mtomcs/mfaf020","DOIUrl":"10.1093/mtomcs/mfaf020","url":null,"abstract":"<p><p>Zinc is central to the function of many proteins, yet the mechanisms of zinc homeostasis and their interplay with other cellular systems remain underexplored. In this study, we employ data-dependent acquisition (DDA) and data-independent acquisition (DIA) mass spectrometry to investigate proteome changes in Pseudomonas aeruginosa under conditions of different zinc availability. Using both methods, we detected a combined 2143 unique proteins, 1578 of which were identified by both DDA and DIA. We demonstrated that most of the previously described Zn homeostasis systems exhibit proteomic responses that follow similar trends to those seen in transcriptomics studies. Furthermore, changes in abundance of multiple Zn-metalloproteins and Zn-independent homologs were clearly observable, with respective increases and decreases when Zn was provided, though the magnitude of these changes varied. Most of the Zn-metalloproteins observed were located in one of two Zur-regulated operons between PA5534 and PA5541. This study provides a view of Zn homeostasis mechanisms that is complementary to existing transcriptomics investigations: as gene transcripts are not strictly proportional to the actual distribution of proteins within a cell, analysis of the proteome offers another way to assess the relative use and importance of similar or ostensibly redundant systems in different conditions and can highlight shifts in metal prioritization between metalloproteins.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A conserved aspartate residue in [4Fe-4S]-containing HypD is required for [NiFe]-cofactor biosynthesis and for efficient interaction of the HypCD scaffold complex with HypE.","authors":"Alexander Haase, Christian Arlt, Maximilian Hardelt, Andrea Sinz, R Gary Sawers","doi":"10.1093/mtomcs/mfaf014","DOIUrl":"10.1093/mtomcs/mfaf014","url":null,"abstract":"<p><p>Six Hyp (A through F) proteins synthesize the NiFe(CN)2CO cofactor found in all [NiFe]-hydrogenases. The Fe(CN)2CO moiety of this cofactor is assembled on a separate scaffold complex comprising HypC and HypD. HypE and HypF generate the cyanide ligands from carbamoyl phosphate by converting the carbamoyl moiety to a thiocyanate associated with HypE's C-terminal cysteine residue, within a conserved 'PRIC' motif. Here, we identify amino acid residue D98 in the central cleft of HypD to be required for biosynthesis of the Fe(CN)2CO moiety and for optimal interaction of HypD with HypE. Construction of a D98A amino acid variant of HypD caused near-complete loss of hydrogenase activity in anaerobically grown Escherichia coli cells, while exchange of the structurally proximal, but non-conserved, residue S356 on HypD, did not. Native mass spectrometric analysis of the anaerobically purified HypC-HypDD98A scaffold complex revealed only a low amount of the bound Fe(CN)2CO group. Western blotting experiments revealed that purified scaffold complexes between either HypC or HybG (a paralogue of HypC) with HypD-D98A showed a strongly impaired interaction with HypE. Examination of the HypCDE complex crystal structure from Thermococcus kodakarensis revealed that D98 of HypD lies within a cleft through which the C-terminus of HypE can access the bound iron ion on HypCD. Alphafold3 predictions suggest that the D98 residue interacts with the arginine residue of the 'PRIC' motif at the C-terminus of HypE to position the modified terminal cysteine residue precisely for delivery of cyanide to the iron ion associated with the HypCD complex.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthesis and assembly of hydrogenase [NiFe]-cofactor: recent advances and perspectives.","authors":"R Gary Sawers, Maximilian Hardelt, Alexander Haase, Dorothea Lubek","doi":"10.1093/mtomcs/mfaf015","DOIUrl":"10.1093/mtomcs/mfaf015","url":null,"abstract":"<p><p>The large subunit of all [NiFe]-hydrogenases in bacteria and archaea has a heterobimetallic NiFe(CN)2CO cofactor coordinated by four cysteine residues. The iron ion has two cyanides and a carbon monoxide as diatomic ligands. Six ancillary Hyp (ABCDEF) proteins are necessary for anaerobic synthesis of this cofactor, while under oxic conditions at least one further protein, HypX, is required for CO synthesis. The Fe(CN)2CO moiety of the cofactor is synthesized on a separate HypCD scaffold complex. Nickel is inserted into the apo-large subunit only after Fe(CN)2CO has been introduced. Recent biochemical and structural studies have significantly advanced our understanding of cofactor biosynthesis for these important metalloenzymes. Despite these gains in mechanistic insight, many questions still remain, the most pressing of which is the origin of the CO ligand in anaerobic microorganisms. This minireview provides an overview of the current status of this research field and highlights recent advances and unresolved issues.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc-mediated dynamics of CD4/CD8α co-receptors and Lck kinase: implications for zinc homeostasis, immune response, and biotechnological innovations.","authors":"Anna Kocyła, Artur Krężel","doi":"10.1093/mtomcs/mfaf018","DOIUrl":"10.1093/mtomcs/mfaf018","url":null,"abstract":"<p><p>Zinc (Zn²⁺) plays a pivotal role in T-cell activation by modulating the interactions between the co-receptors CD4 and CD8α and the Src-family kinase Lck. A central structural feature in this regulation is the zinc clasp, a Zn²⁺-mediated CD4/CD8α-Lck receptor interface that stabilizes these complexes during T cell receptor signaling. Recent findings reveal that the stability of CD4-Lck and CD8α-Lck complexes is differentially regulated by Zn²⁺, which acts as a dynamic signaling molecule during T-cell activation. Here, we discuss the structural dynamics of these interactions and the impact of Zn²⁺ on CD4 dimerization, palmitoylation, and membrane interactions, which are crucial for effective T-cell responses. These mechanisms underscore a broader framework in which zinc biology intersects with co-receptor-Lck coupling to guide T-cell development, lineage fidelity, and functional specialization. Beyond immunobiology, zinc-dependent protein-protein interactions offer promising opportunities for biotechnological innovation, particularly in the design of molecular systems that exploit zinc-mediated structural control.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenoneine scavenges hydroxyl radicals by self-oxidation in hydrogen peroxide and by forming seleninic acid, which is reduced back to selenoneine.","authors":"Takuya Seko, Hajime Uchida, Shintaro Imamura, Kenji Ishihara, Yumiko Yamashita, Michiaki Yamashita","doi":"10.1093/mtomcs/mfaf016","DOIUrl":"10.1093/mtomcs/mfaf016","url":null,"abstract":"<p><p>Selenoneine (SEN), a selenium analog of ergothioneine (EGT), is widely distributed in marine fish and is a strong radical scavenger. Electron spin resonance spectrometry showed that SEN monomer and dimer directly scavenged ·OH generated by irradiating hydrogen peroxide (H2O2) with ultraviolet light. The radical scavenging capacity was stronger for SEN monomer, dimer, and EGT in that order. Mass spectrometry analyses revealed that the monomer and dimer were oxidized to SEN seleninic acid (SEN-seleninic acid) in the presence of H2O2, and that SEN-seleninic acid was reduced to SEN monomer by reduced glutathione (GSH). These reactions proceeded at physiological concentrations of H2O2 and GSH. Our findings suggest that SEN scavenges ·OH directly by a rapid, repetitive nonenzymatic reaction via self-oxidation and by its reduction back to SEN.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}