A ubiquitous metal, difficult to track: towards an understanding of the regulation of titanium(IV) in humans
Molecular mechanisms in the body regulate the cytotoxic properties of titanium(IV) such that Ti(IV) could be bioavailable for cellular functions.
Iron acquisition in fungal pathogens of humans
Fungal pathogens of humans acquire iron by high affinity reductive uptake, the use of siderophores, and by heme acquisition. These systems contribute to virulence to different extents in the pathogens.
Copper trafficking to the secretory pathway
Copper (Cu) is indispensible for growth and development of human organisms.
The emerging role of lysosomes in copper homeostasis
The lysosomal system operates as a focal point where a number of important physiological processes such as endocytosis, autophagy and nutrient sensing converge.
Defining potential roles of Pb2+ in neurotoxicity from a calciomics approach
Metal ions play crucial roles in numerous biological processes, facilitating biochemical reactions by binding to various proteins.
Application of imaging mass spectrometry approaches to facilitate metal-based anticancer drug research
Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems.
The biological chemistry of the transition metal “transportome” of Cupriavidus metallidurans
The metal transportome of Cupriavidus metallidurans. The cell of the Gram-negative bacterium is shown with the outer membrane (outermost grey line), the inner membrane lining the cytoplasm (light yellow) and the periplasm in-between. The number of metal atoms per cell is shown in the middle of the cell. Metal uptake and efflux systems for transition metal are indicated.
Handling of nutrient copper in the bacterial envelope
The insertion of copper into bacterial cuproenzymes in vivo does not always require a copper-binding metallochaperone – why?
From sea squirts to squirrelfish: facultative trace element hyperaccumulation in animals
Facultative trace element hyperaccumulation in animals is reviewed, examining mechanisms of uptake and accumulation, and biological roles.
Aquaporins in cancer development: opportunities for bioinorganic chemistry to contribute novel chemical probes and therapeutic agents
Metal ions and complexes can interfere with the transcellular water flow but also with the cellular transport of glycerol and hydrogen peroxide, via inhibition of the ubiquitous aquaporin channels.
Human Mn-superoxide dismutase inactivation by peroxynitrite: a paradigm of metal-catalyzed tyrosine nitration in vitro and in vivo
Nitration of human MnSOD at active site Tyr34 represents a biologically-relevant oxidative post-translational modification that causes enzyme inactivation.
Interaction of Na+, K+, Mg2+ and Ca2+ counter cations with RNA
Data on the location of alkaline and alkaline earth ions at RNA from crystallography, spectroscopy and computational modeling are reviewed.
Recent structural insights into the function of copper nitrite reductases
Copper nitrite reductases (CuNiRs) catalyse the reduction of nitrite to nitric oxide as part of the denitrification pathway. In this review, we describe insights into CuNiR function from structural studies.
Biosynthetic considerations of triscatechol siderophores framed on serine and threonine macrolactone scaffolds
The biosyntheses of a family of enterobactin variants – amino acid substitution, insertion, and derivatization, and macrolactone expansion – is reviewed.
Ferrous iron efflux systems in bacteria
Iron efflux transporters play a critical role in protecting cells from iron intoxication.
Iron and inflammation – the gut reaction
Intestinal inflammation dysregulates iron metabolism and impairs erythropoiesis, leading to the development of anemia.
The organoarsenical biocycle and the primordial antibiotic methylarsenite
Bacteria produce the primordial antibiotic MAs(III) with the arsM gene, and other bacteria have arsI, arsH or arsP resistance genes.
Ceruloplasmin and other copper binding components of blood plasma and their functions: an update
We know that blood plasma contains many proteins and also other components that bind copper.
Lead neurotoxicity: exploring the potential impact of lead substitution in zinc-finger proteins on mental health
This critical review focuses on one possible link between the cellular biology of lead and its neurotoxic effects: the link between Pb2+ substitution for Zn2+ in zinc-finger proteins and mental illness in adulthood.
The contribution of zinc to platelet behaviour during haemostasis and thrombosis
Platelets are known to be activated by exogenous zinc. Herein we discuss the potential routes for zinc entry and the role of zinc–protein interactions in platelet activation.
Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity
A review of iron and cadmium transport by renal tubules highlighting common pathways and differences with their implications for health and disease.
The affinity of MhuD for heme is consistent with a heme degrading function in vivo
MhuD forms an enzymatically-active 1 : 1 complex with heme at nanomolar concentrations of labile heme and an inactive 1 : 2 complex at micromolar concentrations.
Interaction of Cu(I) with the Met-X3-Met motif of alpha-synuclein: binding ligands, affinity and structural features
Coordination environment and conformational consequences of Cu(I) binding at Met-X3-Met site of AcαS.
Duodenal cytochrome b (Cybrd1) ferric reductase functional studies in cells
A single nucleotide polymorphism (rs10455) in the last exon of the Dcytb gene in C282Y hemochromatosis subjects exhibited increased ferric reductase activity in transgenic CHO cells.
A systems biology approach reveals new endoplasmic reticulum-associated targets for the correction of the ATP7B mutant causing Wilson disease
This study provides new insights into understanding the interplay between ER quality control and copper transport mechanisms in Wilson disease.
High-resolution complementary chemical imaging of bio-elements in Caenorhabditis elegans
A unified approach to chemical imaging was used to spatially profile essential bio-elements in Caenorhabditis elegans.
The role of cysteine and sulfide in the interplay between microbial Hg(II) uptake and sulfur metabolism
Mercury uptake by E. coli in the presence of excess cysteine is facilitated by the biodegradation of cysteine to sulfide and the formation of mercury sulfide species. The deletion of a key cysteine desulfhydrase gene (decR) limits the uptake of mercury in the presence of excess cysteine.
Investigation of the calcium-induced activation of the bacteriophage T5 peptidoglycan hydrolase promoting host cell lysis
Bacteriophage T5 endolysin could be activated by Ca2+ in the periplasm of the host cell, thereby promoting bacterial lysis.
Ferritin exhibits Michaelis–Menten behavior with oxygen but not with iron during iron oxidation and core mineralization
Iron uptake into mammalian ferritins reveals oxygen (but not iron) saturation kinetics and physiologically relevant Km,O2 values.
Active uptake of hydrophilic copper complex Cu(II)–TETA in primary cultures of neonatal rat cardiomyocytes
Cu(II)–TETA is transported across the cell membrane via an unknown ATP-dependent and CTR1-independent process.
Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue
Ruthenium arene anticancer complexes bind to human peroxiredoxin I, leading to oxidation of thiolate and failure of forming a disulfide bond.
Cisplatin reacts with histone H1 and the adduct forms a ternary complex with DNA
The histone H1 readily reacts with cisplatin and the adduct can form H1–cisplatin–DNA ternary complexes. Interestingly, cisplatin is more prone to form H1–Pt–DNA ternary complexes than trans-oriented platinum agents.
A gold(I) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic drug: comparative studies with different gold metallodrugs
A stable gold(I) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic metallodrug.
The third pillar of metal homeostasis in Cupriavidus metallidurans CH34: preferences are controlled by extracytoplasmic function sigma factors
In C. metallidurans, a network of 11 extracytoplasmic function sigma factors forms the third pillar of metal homeostasis acting in addition to the metal transportome and metal repositories as the first and second pillar.
Multifunctional Pt(IV) complexes containing a glutathione S-transferase inhibitor lead to enhancing anticancer activity and preventing metastasis of osteosarcoma cells
Several Pt(IV) prodrugs conjugated with a glutathione S-transferase (GST) inhibitor were studied with the purpose of preventing the metastasis of osteosarcoma.
Mouse metallothionein-1 and metallothionein-2 are not biologically interchangeable in an animal model of multiple sclerosis, EAE
Mice treated daily with MT2 (but not MT1) showed a significant amelioration of the clinical course of experimental autoimmune encephalomyelitis (EAE).
Copper deficiency-induced anemia is caused by a mitochondrial metabolic reprograming in erythropoietic cells
Copper deficiency reprograms mitochondrial metabolism, which becomes less oxidative, to favor cell expansion over cell differentiation.
Characterization of the metal status of natively purified alpha-synuclein from human blood, brain tissue, or recombinant sources using size exclusion ICP-MS reveals no significant binding of Cu, Fe or Zn
The binding of Cu, Fe or Zn to alpha-synuclein has been implicated in neurodegenerative disease, such as Parkinson's.
Time-dependent shotgun proteomics revealed distinct effects of an organoruthenium prodrug and its activation product on colon carcinoma cells
The target spectrum and cellular effects of a metallo-prodrug can be separated from its activated species by time-dependent shotgun proteomics.
The cellular economy of the Saccharomyces cerevisiae zinc proteome
We cataloged the zinc proteome of Saccharomyces cerevisiae and analyzed how it responds to changing zinc status.
Antimicrobial action of calprotectin that does not involve metal withholding
The metal (red) bound form of calprotectin (green) binds Borrelia burgdorferi and inhibits pathogen growth without metal withholding.
Copper reduction and dioxygen activation in Cu–amyloid beta peptide complexes: insight from molecular modelling
Alzheimer's disease (AD) involves a number of factors including an anomalous interaction of copper with the amyloid peptide (Aβ), inducing oxidative stress with radical oxygen species (ROS) production through a three-step cycle in which O2 is gradually reduced to superoxide, oxygen peroxide and finally OH radicals.
miRNA-182-5p, via HIF2α, contributes to arsenic carcinogenesis: evidence from human renal epithelial cells
Overexpression of HIF2α via miR-182-5p suppression is involved in arsenic-induced malignant transformation of human renal epithelial cells.
Altered zinc balance in the Atp7b−/− mouse reveals a mechanism of copper toxicity in Wilson disease
Copper accumulation in the Atp7b−/− model of Wilson disease impacts zinc distribution.
The type 4 metallothionein from Brassica napus seeds folds in a metal-dependent fashion and favours zinc over other metals
Rapeseed MT4 only folds properly in the presence of Zn2+ and thus may serve as a selectivity filter for metal accumulation in plant embryos.
A histidine-rich Pseudomonas metallothionein with a disordered tail displays higher binding capacity for cadmium than zinc
The NMR solution structure of a Pseudomonas metallothionein reveals a different binding capacity for ZnII and CdII ions that results in two novel metal-cluster topologies. Replacement of a non-coordinating residue by histidine decreases the kinetic lability of the cluster. All three structures reported show an identical protein fold.
The human iron-proteome
In this work we compiled a comprehensive list of all human iron-proteins based on bioinformatics predictions and analyzed their functional roles, distribution within cell compartments and involvement in disease.
High affinity interactions of Pb2+ with synaptotagmin I
Pb2+ binds C2 domains with high affinity, desensitizes them to Ca2+, and supports their membrane interactions.
Overexpression of the mitochondrial Mg channel MRS2 increases total cellular Mg concentration and influences sensitivity to apoptosis
Mitochondrial Mg channel MRS2 overexpression influences Mg concentration and sensitivity to apoptosis.
Low-molecular-mass iron in healthy blood plasma is not predominately ferric citrate
The labile iron pool in blood consists of complexes with masses of 400–2500 Daltons that are not ferric citrate.
Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease
Coregistering quantitative high-resolution metal imaging with fluorescence imaging identifies copper accumulation in megamitochondria within intact neuroretinal slices.
Nickel(II) inhibits the oxidation of DNA 5-methylcytosine in mammalian somatic cells and embryonic stem cells
Nickel(II) inhibits Tet-mediated oxidation of DNA 5-methylcytosine in mammalian cells.
The antioxidant 2,6-di-tert-butylphenol moiety attenuates the pro-oxidant properties of the auranofin analogue
Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry.
A cytosolic copper storage protein provides a second level of copper tolerance in Streptomyces lividans
A cytosolic copper storage protein has been identified in Streptomyces lividans and plays a role in copper tolerance once the first layer of copper resistance becomes saturated.
Calcium isotope signature: new proxy for net change in bone volume for chronic kidney disease and diabetic rats
Herein, we measure the Ca isotope ratios (44Ca/42Ca and 43Ca/42Ca) in serum and bone samples collected from rats with chronic kidney disease (CKD) or diabetes mellitus (DM).
Mechanisms of iron and copper–frataxin interactions
Investigation of the mechanisms of mitochondrial metal binding to frataxin in vitro.
BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana
BTS family members negatively regulate the Fe deficiency response; mutants have increased Fe levels and tolerance to Fe deficiency.
Reactivity of U-associated osteopontin with lactoferrin: a one-to-many complex
A highly-simplified scenario of LF/U-fOPN interaction. The U content of the U-fOPN complexes refers to the CE-ICP/MS experiments.
Decoding the anticancer activity of VO-clioquinol compound: the mechanism of action and cell death pathways in human osteosarcoma cells
Vanadium compounds were studied in recent years by considering them as a representative of a new class of non-platinum metal anticancer drugs.
Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease
One dual-function (2) and one first-generation (9) conjugate of the Fe(III) chelator desferrioxamine B (DFOB, 1) showed significant rescue of neurons in the MPTP mouse model of Parkinson's disease.
Inhibiting the BfrB:Bfd interaction in Pseudomonas aeruginosa causes irreversible iron accumulation in bacterioferritin and iron deficiency in the bacterial cytosol
The BfrB:Bfd interaction enables a dynamic equilibrium between free cytosolic Fe2+ and Fe3+ in BfrB, which functions as a buffer to oppose large fluctuations of free cytosolic Fe2+.
Metabolomic analysis of the effects of cadmium and copper treatment in Oryza sativa L. using untargeted liquid chromatography coupled to high resolution mass spectrometry and all-ion fragmentation
Evaluation of the effect of metal exposure (cadmium/copper) on metabolic pathways of rice.
Stepwise copper(I) binding to metallothionein: a mixed cooperative and non-cooperative mechanism for all 20 copper ions
Speciation resulting from 20 bimolecular, sequential reactions involving 20 Cu(I) ions binding to metallothionein at different pH-values is reported.
Structure–function studies of acinetobactin analogs
The siderophore pre-acinetobactin undergoes a facile 5-exo-tet cyclization to enhance iron acquisition and virulence of the pathogenic producer Acinetobacter baumannii.
Unique structural properties of DNA interstrand cross-links formed by a new antitumor dinuclear Pt(II) complex
Unique long-range DNA interstrand cross-links of a dinuclear platinum complex formed in the 3′–3′ direction affect its antitumor effects.
High-affinity metal binding by the Escherichia coli [NiFe]-hydrogenase accessory protein HypB is selectively modulated by SlyD
SlyD activates the release of nickel and blocks the release of zinc from the high-affinity metal site of HypB.
The effect of metalloprotein inhibitors on cellular metal ion content and distribution
Synchrotron X-ray fluorescence microscopy (SXRF) data reveal that metalloprotein inhibitors (MPi) do not significantly perturb cellular Zn content or distribution.
Biochemical characterization of the selenoproteome in Gallus gallus via bioinformatics analysis: structure–function relationships and interactions of binding molecules
Knowledge about mammalian selenoproteins is increasing.
Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production
Aβ oxidation due to HO˙ production by Cu–Aβ/ascorbate changes copper coordination and leads to the self-enhancement of HO˙ production and release.
The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia
Copper loss in ischemic myocardium makes a critical contribution to the suppression of HIF-1-regulated angiogenesis.
About this collection
This themed collection features articles published in Metallomics marked as HOT by the handling editor or as recommended by referees. Congratulations to all the authors whose articles are featured.