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Potassium manganese hexacianoferrate has been prepared by co‐precipitation from manganese (II) chloride and potassium citrate, with chemical analysis yielding the formula K1.72Mn[Fe(CN)6]0.92□0.08 ⋅ 1.1H2O (KMnHCF). Its X‐ray diffraction pattern is consistent with a monoclinic structure (space group P 21/n, no. 14) with cell parameters a=10.1202(6)Å, b=7.2890(5)Å, c=7.0193(4)Å, and β=89.90(1)°. Its redox behavior has been studied in magnesium containing electrolytes. Both K+ ions deintercalated from the structure upon oxidation and contamination with Na+ ions coming from the separator were found to interfere in the electrochemical response. In the absence of alkaline ions, pre‐oxidized manganese hexacianoferrate showed reversible magnesium intercalation, and the process has been studied by operando synchrotron X‐ray diffraction. The location of Mg2+ ions in the crystal structure was not possible with the available experimental data. Still, density functional theory simulations indicated that the most favorable position for Mg2+ intercalation is at 32f sites (considering a pseudo cubic F m‐3m phase), which are located between 8c and Mn sites. [ABSTRACT FROM AUTHOR]

The development of high energy density battery technologies based on divalent metals as the negative electrode is very appealing. Ca and Mg are especially interesting choices due to their combination of low standard reduction potential and natural abundance. One particular problem stalling the technological development of these batteries is the low efficiency of plating/stripping at the negative electrode, which relates to several factors that have not yet been looked at systematically; the nature/concentration of the electrolyte, which determines the mass transport of electro‐active species (cation complexes) toward the electrode; the possible presence of passivation layers, which may hinder ionic transport and hence limit electrodeposition; and the mechanisms behind the charge transfer leading to nucleation/growth of the metal. Different electrolytes are investigated for Mg and Ca, with the presence/absence of chlorides in the formulation playing a crucial role in the cation desolvation. From a R&D point‐of‐view, proper characterization alongside modeling is crucial to understand the phenomena determining the mechanisms of the plating/stripping processes. The state‐of‐the‐art is here presented together with a short perspective on the influence of the cation solvation also on the positive electrode and finally an attempt to define guidelines for future research in the field. [ABSTRACT FROM AUTHOR]

Background: Lysinuric protein intolerance is a rare autosomal disorder caused by mutations in the Slc7a7 gene that lead to impaired transport of neutral and basic amino acids. The gold standard treatment for lysinuric protein intolerance involves a low-protein diet and citrulline supplementation. While this approach partially improves cationic amino acid plasma levels and alleviates some symptoms, long-term treatment is suggested to be detrimental and may lead to life-threatening complications characterized by a wide range of hematological and immunological abnormalities. The specific cause of these hematopoietic defects-whether intrinsic to hematopoietic cells or driven by external factors-remains unclear. Given the limitations of current citrulline-based treatments and the unknown role of SLC7A7 in red blood cell production, there is an urgent need to investigate the pathways affected by SLC7A7 deficiency., Methods: We employed total inducible and cell type-specific Slc7a7 knockout mouse models to determine whether the hematological abnormalities observed in LPI are due to the loss of Slc7a7 function in hematopoietic cells. We analyzed erythropoiesis in these mice and performed bone marrow transplantation experiments to assess the role of Slc7a7 in erythroblasts and myeloid cells. The statistical significance of differences between groups was evaluated via standard statistical tests, including Student's t test and ANOVA., Results: Whole-body Slc7a7 knockout mice presented impaired erythropoiesis. However, this defect was not replicated in mice with Slc7a7 deficiency restricted to erythroblasts or myeloid cells, suggesting that the observed hematopoietic abnormalities are not due to intrinsic Slc7a7 loss in these cell types. Additionally, bone marrow transplants from control mice did not rescue the hematopoietic defects in Slc7a7-deficient mice, nor did the transplantation of Slc7a7-deficient cells induce defects in control recipients. Further investigation indicated that defective erythropoiesis is linked to impaired erythropoietin production in the kidney and subsequent iron overload., Conclusions: The hematopoietic defects in the Lysinuric protein intolerance mouse model are not caused by intrinsic Slc7a7 loss in hematopoietic cells but rather by impaired erythropoietin production in the kidney. This finding opens potential avenues for therapeutic strategies targeting erythropoietin production to address hematological abnormalities in humans with lysinuric protein intolerance., Competing Interests: Declarations. Ethical approval and consent to participate: All animal work was conducted following established guidelines. The project (DARP No. 9177) was favorably assessed by the Institutional Animal Care and Use Committee of the Parc Científic de Barcelona (IACUC-PCB), and the IACUC considered that the project complied with standard ethical regulations and met the requirements of current applicable legislation (RD 53/2013 Council Directive; 2010/63/UE; Order 214/1997/GC. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

L-Amino acid transporters (LATs) play a key role in a wide range of physiological processes. Defects in LATs can lead to neurological disorders and aminoacidurias, while the overexpression of these transporters is related to cancer. BasC is a bacterial LAT transporter with an APC fold. In this study, to monitor the cytoplasmic motion of BasC, we developed a single-molecule Förster resonance energy transfer assay that can characterize the conformational states of the intracellular gate in solution at room temperature. Based on combined biochemical and biophysical data and molecular dynamics simulations, we propose a model in which the conserved lysine residue in TM5 supports TM1a to explore both open and closed states within the cytoplasmic gate under apo conditions. This equilibrium can be altered by substrates, mutation of conserved lysine 154 in TM5, or a transport-blocking nanobody interacting with TM1a. Overall, these findings provide insights into the transport mechanism of BasC and highlight the significance of the lysine residue in TM5 in the cytoplasmic gating of LATs., (© The Author(s) 2025. Published by Oxford University Press on behalf of National Academy of Sciences.)

Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and human skeletal muscle. Importantly, chronic activation of autophagy by muscle-specific overexpression of TRP53INP2 prevents sarcopenia and the decline of muscle function in mice. Acute re-expression of TRP53INP2 in aged mice also improves muscle atrophy, enhances mitophagy, and reduces ROS production. In humans, high levels of TP53INP2 in muscle are associated with increased muscle strength and healthy aging. Our findings highlight the relevance of an active muscle autophagy in the maintenance of muscle mass and prevention of sarcopenia. Abbreviation : ATG7: autophagy related 7; BMI: body mass index; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ROS: reactive oxygen species; TP53INP2: tumor protein p53 inducible nuclear protein 2; WT: wild type.

Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that efficiently transports glycine and D-serine, and thus has a regulatory role in the central nervous system. Here we use cryoEM, ligand-binding simulations, mutagenesis, transport assays, and molecular dynamics to define human Asc1/CD98hc determinants for substrate specificity and gain insights into the mechanisms that govern substrate translocation by exchange and facilitated diffusion. The cryoEM structure of Asc1/CD98hc is determined at 3.4-3.8 Å resolution, revealing an inward-facing semi-occluded conformation. We find that Ser 246 and Tyr 333 are essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. Taken together, these results reveal the structural bases for ligand binding and transport features specific to human Asc1., (© 2024. The Author(s).)

Potassium manganese hexacianoferrate has been prepared by co-precipitation from manganese (II) chloride and potassium citrate, with chemical analysis yielding the formula K 1.72 Mn[Fe(CN) 6 ] 0.92 □ 0.08  ⋅ 1.1H 2 O (KMnHCF). Its X-ray diffraction pattern is consistent with a monoclinic structure (space group P 2 1 /n, no. 14) with cell parameters a=10.1202(6)Å, b=7.2890(5)Å, c=7.0193(4)Å, and β=89.90(1)°. Its redox behavior has been studied in magnesium containing electrolytes. Both K + ions deintercalated from the structure upon oxidation and contamination with Na + ions coming from the separator were found to interfere in the electrochemical response. In the absence of alkaline ions, pre-oxidized manganese hexacianoferrate showed reversible magnesium intercalation, and the process has been studied by operando synchrotron X-ray diffraction. The location of Mg 2+ ions in the crystal structure was not possible with the available experimental data. Still, density functional theory simulations indicated that the most favorable position for Mg 2+ intercalation is at 32f sites (considering a pseudo cubic F m-3m phase), which are located between 8c and Mn sites., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the MFN2 splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of MFN2 produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology, whereas ERMIT2 localized at the ER-mitochondria interface and interacted with mitochondrial mitofusins to tether ER and mitochondria. This tethering allowed efficient mitochondrial calcium ion uptake and phospholipid transfer. Expression of ERMIT2 ameliorated the ER stress, inflammation, and fibrosis typical of liver-specific Mfn2 knockout mice. Thus, ER-specific MFN2 variants display entirely extramitochondrial MFN2 functions involved in interorganellar tethering and liver metabolic activities.

Brown adipose tissue (BAT) thermogenesis affects energy balance, and thereby it has the potential to induce weight loss and to prevent obesity. Here, we document a macroautophagic/autophagic-dependent mechanism of peroxisome proliferator-activated receptor gamma (PPARG) activity regulation that induces brown adipose differentiation and thermogenesis and that is mediated by TP53INP2. Disruption of TP53INP2-dependent autophagy reduced brown adipogenesis in cultured cells. In vivo specific- tp53inp2 ablation in brown precursor cells or in adult mice decreased the expression of thermogenic and mature adipocyte genes in BAT. As a result, TP53INP2-deficient mice had reduced UCP1 content in BAT and impaired maximal thermogenic capacity, leading to lipid accumulation and to positive energy balance. Mechanistically, TP53INP2 stimulates PPARG activity and adipogenesis in brown adipose cells by promoting the autophagic degradation of NCOR1, a PPARG co-repressor. Moreover, the modulation of TP53INP2 expression in BAT and in human brown adipocytes suggests that this protein increases PPARG activity during metabolic activation of brown fat. In all, we have identified a novel molecular explanation for the contribution of autophagy to BAT energy metabolism that could facilitate the design of therapeutic strategies against obesity and its metabolic complications.

Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in mitigating such processes and their impact on muscle fitness remain unaddressed. Here we report that opposite mitochondrial morphologies induce distinct inflammatory signatures, caused by differential activation of DNA sensors TLR9 or cGAS. In the context of mitochondrial fragmentation, we demonstrate that mitochondria-endosome contacts mediated by the endosomal protein Rab5C are required in TLR9 activation in cells. Skeletal muscle mitochondrial fragmentation promotes TLR9-dependent inflammation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which improved upon chronic anti-inflammatory treatment. Taken together, our data demonstrate that mitochondrial dynamics is key in preventing sterile inflammatory responses, which precede the development of muscle atrophy and impaired physical performance. Thus, we propose the targeting of mitochondrial dynamics as an approach to treating disorders characterized by chronic inflammation and mitochondrial dysfunction., (© 2023. The Author(s).)

Magnesium batteries have attracted great attention as an alternative to Li-ion batteries but still suffer from limited choice of positive electrode materials. V 2 O 5 exhibits high theoretical capacities, but previous studies have been mostly limited to α-V 2 O 5 . Herein, we report on the β-V 2 O 5 polymorph as a Mg intercalation electrode. The structural changes associated with the Mg 2+ (de-) intercalation were analyzed by a combination of several characterization techniques: in situ high resolution X-ray diffraction, scanning transmission electron microscopy, electron energy-loss spectroscopy, and X-ray absorption spectroscopy. The reversible capacity reached 361 mAh g -1 , the highest value found at room temperature for V 2 O 5 polymorphs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Heteromeric amino acid transporters (HATs) are one of the ten types of amino acid transporters present in the human body. Growing interest in the pathophysiological role of this group of transporters in rare and complex diseases and cancer has brought about the recent resolution of various structures of human HATs and bacterial homologues at atomic level. This knowledge sheds light on the mechanisms of transport used by these molecules. Here, we discuss the molecular bases underlying substrate specificity, binding asymmetry, and the impact of disease-causing mutations on transporter biogenesis and function., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Sarcopenia is one of the main factors contributing to the disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria (MIT) in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BCL2 interacting protein 3 (BNIP3) plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of Toll-like receptor 9 (TLR9)-dependent inflammation and activation of the NLRP3 (nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein 3) inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mice and humans. Taken together, our data allow us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key to maintaining muscle health during aging., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)