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1.
MICU1 Confers Protection from MCU-Dependent Manganese Toxicity.
Wettmarshausen, J, Goh, V, Huang, KT, Arduino, DM, Tripathi, U, Leimpek, A, Cheng, Y, Pittis, AA, Gabaldón, T, Mokranjac, D, et al
Cell reports. 2018;(6):1425-1435.e7
Abstract
The mitochondrial calcium uniporter is a highly selective ion channel composed of species- and tissue-specific subunits. However, the functional role of each component still remains unclear. Here, we establish a synthetic biology approach to dissect the interdependence between the pore-forming subunit MCU and the calcium-sensing regulator MICU1. Correlated evolutionary patterns across 247 eukaryotes indicate that their co-occurrence may have conferred a positive fitness advantage. We find that, while the heterologous reconstitution of MCU and EMRE in vivo in yeast enhances manganese stress, this is prevented by co-expression of MICU1. Accordingly, MICU1 deletion sensitizes human cells to manganese-dependent cell death by disinhibiting MCU-mediated manganese uptake. As a result, manganese overload increases oxidative stress, which can be effectively prevented by NAC treatment. Our study identifies a critical contribution of MICU1 to the uniporter selectivity, with important implications for patients with MICU1 deficiency, as well as neurological disorders arising upon chronic manganese exposure.
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2.
Fabrication of Stabilized Fe⁻Mn Binary Oxide Nanoparticles: Effective Adsorption of 17β-Estradiol and Influencing Factors.
Ning, Q, Yin, Z, Liu, Y, Tan, X, Zeng, G, Jiang, L, Liu, S, Tian, S, Liu, N, Wang, X
International journal of environmental research and public health. 2018;(10)
Abstract
Fe⁻Mn binary oxide nanoparticles (FMBON) were reported to be high performance as adsorbent for pollutants removal from aqueous solution. However, there are still limitations in practice application due to the FMBON tend to aggregate into the micro millimeter level. In order to avoid the agglomeration of nanoparticles, this work synthesized the stabilized Fe⁻Mn binary oxide nanoparticles (CMC-FMBON) by using water-soluble carboxymethyl celluloses (CMC) as the stabilizer. The characteristics of CMC-FMBON and FMBON were measured by using Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and Zeta potential. This work systematically investigated the adsorption capacity of CMC-FMBON for 17β-estradiol (E2) and the influences of external environmental factors on E2 removal. The results indicated that CMC-FMBON had much smaller particles, wider dispersion and larger surface area than the FMBON. CMC-FMBON showed better adsorption performance for E2 than FMBON with the maximum adsorption capacity of CMC-FMBON and FMBON were 124.10 and 98.14 mg/g at 298 K, respectively. The experimental data can be well fitted by the model of pseudo-second-order and Langmuir model. The E2 removal by CMC-FMBON was obviously dependent on pH with the maximum adsorption occurring when the pH was acidic. The removal capacity of CMC-FMBON increased when enhancing ionic strength in solution. Background electrolytes promoted slightly E2 adsorption process whereas the presence of humic acid inhibited the E2 removal. π-π interactions, hydrogen bonds, and oxidation might be responsible for E2 removal. This research suggested that the CMC-FMBON has been considered to be a cost-efficient adsorbent for removing E2 from water.
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3.
Importing Manganese into the Chloroplast: Many Membranes to Cross.
Krieger-Liszkay, A, Thomine, S
Molecular plant. 2018;(9):1109-1111
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4.
Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses.
Ceballos-Laita, L, Gutierrez-Carbonell, E, Takahashi, D, Abadía, A, Uemura, M, Abadía, J, López-Millán, AF
Journal of proteomics. 2018;:117-129
Abstract
The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 70% of them predicted as secretory. Iron and Mn deficiencies caused statistically significant and biologically relevant abundance changes in 119 and 118 xylem sap proteins, respectively. In both deficiencies, metabolic pathways most affected were protein metabolism, stress/oxidoreductases and cell wall modifications. First, results suggest that Fe deficiency elicited more stress responses than Mn deficiency, based on the changes in oxidative and proteolytic enzymes. Second, both nutrient deficiencies affect the secondary cell wall metabolism, with changes in Fe deficiency occurring via peroxidase activity, and in Mn deficiency involving peroxidase, Cu-oxidase and fasciclin-like arabinogalactan proteins. Third, the primary cell wall metabolism was affected by both nutrient deficiencies, with changes following opposite directions as judged from the abundances of several glycoside-hydrolases with endo-glycolytic activities and pectin esterases. Fourth, signaling pathways via xylem involving CLE and/or lipids as well as changes in phosphorylation and N-glycosylation also play a role in the responses to these stresses. Biological significance In spite of being essential for the delivery of nutrients to the shoots, our knowledge of xylem responses to nutrient deficiencies is very limited. The present work applies a shotgun proteomic approach to unravel the effects of Fe and Mn deficiencies on the xylem sap proteome. Overall, Fe deficiency seems to elicit more stress in the xylem sap proteome than Mn deficiency, based on the changes measured in proteolytic and oxido-reductase proteins, whereas both nutrients exert modifications in the composition of the primary and secondary cell wall. Cell wall modifications could affect the mechanical and permeability properties of the xylem sap vessels, and therefore ultimately affect solute transport and distribution to the leaves. Results also suggest that signaling cascades involving lipid and peptides might play a role in nutrient stress signaling and pinpoint interesting candidates for future studies. Finally, both nutrient deficiencies seem to affect phosphorylation and glycosylation processes, again following an opposite pattern.
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5.
Oxidation catalysis by iron and manganese porphyrins within enzyme-like cages.
Chino, M, Leone, L, Zambrano, G, Pirro, F, D'Alonzo, D, Firpo, V, Aref, D, Lista, L, Maglio, O, Nastri, F, et al
Biopolymers. 2018;(10):e23107
Abstract
Inspired by natural heme-proteins, scientists have attempted for decades to design efficient and selective metalloporphyrin-based oxidation catalysts. Starting from the pioneering work on small molecule mimics in the late 1970s, we have assisted to a tremendous progress in designing cages of different nature and complexity, able to accommodate metalloporphyrins. With the intent of tuning and controlling their reactivity, more and more sophisticated and diverse environments are continuously exploited. In this review, we will survey the current state of art in oxidation catalysis using iron- and manganese-porphyrins housed within designed or engineered protein cages. We will also examine the innovative metal-organic framework (MOF) systems, exploited to achieving an enzyme-like environment around the metalloporphyrin cofactor.
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6.
Effects of manganese toxicity on the protein profile of tomato (Solanum lycopersicum) roots as revealed by two complementary proteomic approaches, two-dimensional electrophoresis and shotgun analysis.
Ceballos-Laita, L, Gutierrez-Carbonell, E, Imai, H, Abadía, A, Uemura, M, Abadía, J, López-Millán, AF
Journal of proteomics. 2018;:51-63
Abstract
The aim of this work was to assess the effects of manganese (Mn) toxicity on the proteome of tomato roots using two proteomic approaches, shotgun and two-dimensional electrophoresis. The shotgun approach yielded 367 reliable proteins, whereas the 2-DE approach detected 340 consistent spots. The 2-DE method found 54 proteins changing in relative abundance in the excess Mn treatment, whereas the shotgun detected changes in 118 proteins. Only 7% of the differential proteins were found by both methods, illustrating their complementary nature. Metabolic pathways most affected were protein metabolism, oxido-reductases and signaling. Results support that Mn toxicity alters the protein turnover and impairs energy production in roots, leading to changes in glycolysis, pyruvate metabolism, TCA and oxidative phosphorylation. Excess Mn also induced changes in peroxidases and hydrolases participating in cell wall lignification and suberization and activated plant defense mechanisms, with changes occurring via pathogenesis-related proteins as well as peroxidases. Finally, Mn toxicity elicited regulatory mechanisms and affected the abundance of root nutrient reservoir proteins. The overall analysis of the differential root proteome upon Mn toxicity suggests a general slowdown of metabolic activities, especially energy production, cell wall integrity and protein turnover, which occurs in parallel with increases in stress related proteins.
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7.
Anti-σ factor YlaD regulates transcriptional activity of σ factor YlaC and sporulation via manganese-dependent redox-sensing molecular switch in Bacillus subtilis.
Kwak, MK, Ryu, HB, Song, SH, Lee, JW, Kang, SO
The Biochemical journal. 2018;(13):2127-2151
Abstract
YlaD, a membrane-anchored anti-sigma (σ) factor of Bacillus subtilis, contains a HX3CXXC motif that functions as a redox-sensing domain and belongs to one of the zinc (Zn)-co-ordinated anti-σ factor families. Despite previously showing that the YlaC transcription is controlled by YlaD, experimental evidence of how the YlaC-YlaD interaction is affected by active cysteines and/or metal ions is lacking. Here, we showed that the P yla promoter is autoregulated solely by YlaC. Moreover, reduced YlaD contained Zn and iron, while oxidized YlaD did not. Cysteine substitution in YlaD led to changes in its secondary structure; Cys3 had important structural functions in YlaD, and its mutation caused dissociation from YlaC, indicating the essential requirement of a HX3CXXC motif for regulating interactions of YlaC with YlaD. Analyses of the far-UV CD spectrum and metal content revealed that the addition of Mn ions to Zn-YlaD changed its secondary structure and that iron was substituted for manganese (Mn). The ylaC gene expression using βGlu activity from P yla :gusA was observed at the late-exponential and early-stationary phase, and the ylaC-overexpressing mutant constitutively expressed gene transcripts of clpP and sigH, an important alternative σ factor regulated by ClpXP. Collectively, our data demonstrated that YlaD senses redox changes and elicits increase in Mn ion concentrations and that, in turn, YlaD-mediated transcriptional activity of YlaC regulates sporulation initiation under oxidative stress and Mn-substituted conditions by regulating clpP gene transcripts. This is the first report of the involvement of oxidative stress-responsive B. subtilis extracytoplasmic function σ factors during sporulation via a Mn-dependent redox-sensing molecular switch.
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8.
The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions.
Li, L, Yang, X
Oxidative medicine and cellular longevity. 2018;:7580707
Abstract
Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.
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9.
A fundamental catalytic difference between zinc and manganese dependent enzymes revealed in a bacterial isatin hydrolase.
Sommer, T, Bjerregaard-Andersen, K, Uribe, L, Etzerodt, M, Diezemann, G, Gauss, J, Cascella, M, Morth, JP
Scientific reports. 2018;(1):13104
Abstract
The catalytic mechanism of the cyclic amidohydrolase isatin hydrolase depends on a catalytically active manganese in the substrate-binding pocket. The Mn2+ ion is bound by a motif also present in other metal dependent hydrolases like the bacterial kynurenine formamidase. The crystal structures of the isatin hydrolases from Labrenzia aggregata and Ralstonia solanacearum combined with activity assays allow for the identification of key determinants specific for the reaction mechanism. Active site residues central to the hydrolytic mechanism include a novel catalytic triad Asp-His-His supported by structural comparison and hybrid quantum mechanics/classical mechanics simulations. A hydrolytic mechanism for a Mn2+ dependent amidohydrolases that disfavour Zn2+ as the primary catalytically active site metal proposed here is supported by these likely cases of convergent evolution. The work illustrates a fundamental difference in the substrate-binding mode between Mn2+ dependent isatin hydrolase like enzymes in comparison with the vast number of Zn2+ dependent enzymes.
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10.
Relative association of Rubisco with manganese and magnesium as a regulatory mechanism in plants.
Bloom, AJ, Kameritsch, P
Physiologia plantarum. 2017;(4):545-559
Abstract
Rubisco, the enzyme that constitutes as much as half of the protein in a leaf, initiates either the photorespiratory pathway that supplies reductant for the assimilation of nitrate into amino acids or the C3 carbon fixation pathway that generates carbohydrates. The relative rates of these two pathways depend both on the relative extent to which O2 and CO2 occupies the active site of Rubisco and on whether manganese or magnesium is bound to the enzyme. This study quantified the activities of manganese and magnesium in isolated tobacco chloroplasts and the thermodynamics of binding of these metals to Rubisco purified from tobacco or a bacterium. In tobacco chloroplasts, manganese was less active than magnesium, but Rubisco purified from tobacco had a higher affinity for manganese. The activity of each metal in the chloroplast was similar in magnitude to the affinity of tobacco Rubisco for each. This indicates that, in tobacco chloroplasts, Rubisco associates almost equally with both metals and rapidly exchanges one metal for the other. Binding of magnesium was similar in Rubisco from tobacco and a bacterium, whereas binding of manganese differed greatly between the Rubisco from these species. Moreover, the ratio of leaf manganese to magnesium in C3 plants increased as atmospheric CO2 increased. These results suggest that Rubisco has evolved to improve the energy transfers between photorespiration and nitrate assimilation and that plants regulate manganese and magnesium activities in the chloroplast to mitigate detrimental changes in their nitrogen/carbon balance as atmospheric CO2 varies.