Article
Biochemistry & Molecular Biology
Jingjing Liu, Huimin Chen, Hongkun Lin, Shufen Peng, Li Chen, Xueer Cheng, Ping Yao, Yuhan Tang
Summary: This study found that quercetin can protect against ethanol-induced mitochondrial dysfunction by increasing the expression of the mitochondrial protein frataxin through regulating iron levels.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Cell Biology
Mengyao Xu, Long Ding, Jingjing Liang, Xiao Yang, Yuan Liu, Yingchun Wang, Mei Ding, Xun Huang
Summary: NADK and FASN1 regulate lipid storage and mitochondrial function by manipulating NADPH and fatty acid levels.
Article
Biochemistry & Molecular Biology
Santiago Mansilla, Veronica Tortora, Florencia Pignataro, Santiago Sastre, Ignacio Castro, Ma. Laura Chiribao, Carlos Robello, Ari Zeida, Javier Santos, Laura Castro
Summary: Mitochondrial aconitase (ACO2) is a redox sensor in the tricarboxylic acid cycle, sensitive to reactive oxygen and nitrogen species due to its labile [4Fe-4S](2+) prosthetic group. It has been implicated in aging and pathologies related to mitochondrial dysfunction. Recombinant human ACO2 was expressed and characterized, showing high yield and determining kinetic parameters. ACO2 reacts with various reactive species with different rate constants, and its thermal stability is lower upon cluster oxidation. It was confirmed that frataxin (FXN) can reactivate [3Fe-4S](+)-ACO2 and directly interact with iron. Molecular dynamics simulations revealed differences in protein dynamics based on the Fe-S cluster redox state.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Microbiology
Alzbeta Motyckova, Lubos Voleman, Vladimira Najdrova, Lenka Arbonova, Martin Benda, Vit Dohnalek, Natalia Janowicz, Ronald Malych, Robert Sutak, Thijs J. G. Ettema, Staffan Svard, Courtney W. Stairs, Pavel Dolezal
Summary: This study characterized the late ISC pathway in the simplest mitosomes of Giardia intestinalis and identified a novel BolA1 homologue. However, the absence of the bolA1 gene did not significantly affect the number and capability of mitosomes. Furthermore, no natural client proteins requiring [2Fe-2S] or [4Fe-4S] clusters within the mitosomes were found.
Article
Biochemistry & Molecular Biology
M. Tajes, C. Diez-Lopez, C. Enjuanes, P. Moliner, J. L. Ferreiro, A. Garay, S. Jimenez-Marrero, S. Yun, S. G. Sosa, L. Alcoberro, J. Gonzalez-Costello, E. Garcia-Romero, L. Yanez-Bisbe, B. Benito, J. Comin-Colet
Summary: Iron deficiency is common in patients with heart failure and is associated with poor outcomes. Activation of neurohormones in heart failure leads to changes in iron homeostasis, reduced intracellular iron levels, and impaired mitochondrial function. This suggests that iron may play a role in the pathophysiology of heart failure.
CELL AND BIOSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Miranda K. Culley, Rashmi J. Rao, Monica Mehta, Jingsi Zhao, Wadih El Khoury, Lloyd D. Harvey, Dror Perk, Yi Yin Tai, Ying Tang, Sruti Shiva, Marlene Rabinovitch, Mingxia Gu, Thomas Bertero, Stephen Y. Chan
Summary: Deficiency of iron-sulfur (Fe-S) clusters in the endothelium leads to metabolic rewiring and the development of pulmonary hypertension (PH). Reduction of frataxin (FXN) drives genotoxic stress and senescence in multiple types of pulmonary vascular disease. FXN deficiency affects both mitochondrial and nuclear processes in the endothelium, contributing to pathologic aberrations in metabolism and genomic stability.
VASCULAR PHARMACOLOGY
(2023)
Article
Cell Biology
Juan Hu, Yue Gao, Qian Huang, Yuanyuan Wang, Xiaoyi Mo, Peiyu Wang, Youjing Zhang, Chang Xie, Dongdong Li, Jing Yao
Summary: The study revealed that the lipid raft-associated protein flotillin-1 is a key element in the TRPV2 signaling complex, enhancing the whole-cell current density of TRPV2 by increasing its surface expression levels.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Bowen Huang, Xiang Zhang, Qin Liu, Changming Bai, Chen Li, Chongming Wang, Lusheng Xin
Summary: In this study, the researchers found that OsHV-1 infection in ark clams can suppress the post-transcriptional translation of SbFn by regulating SbIRP-1, thereby evading host iron limitation.
Article
Biochemistry & Molecular Biology
Davide Doni, Marta Meggiolaro, Javier Santos, Gerard Audran, Sylvain R. A. Marque, Paola Costantini, Marco Bortolus, Donatella Carbonera
Summary: Frataxin is a conserved mitochondrial protein involved in iron-sulfur cluster machinery and redox imbalance, potentially interacting with mitochondrial superoxide dismutase. This interaction could play a role in the assembly and protection of FeS clusters against reactive oxygen species.
Article
Biochemistry & Molecular Biology
Lucia D. Espeche, Karl Ellioth Sewell, Ignacio H. Castro, Luciana Capece, Maria Florencia Pignataro, Liliana Dain, Javier Santos
Summary: The study found that replacement of frataxin by glycine at different tryptophan sites resulted in varying effects on iron-sulfur cluster assembly activity, with W155G showing no activity, W168G being fully active, and W173G having significantly decreased activity. Additionally, W173G may exhibit altered motions at the Trp155 site.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Nazli Khodayari, Rejean L. Wang, Regina Oshins, Yuanqing Lu, Michael Millett, Alek M. Aranyos, Sayedamin Mostofizadeh, Yogesh Scindia, Tammy O. Flagg, Mark Brantly
Summary: Alpha-1 antitrypsin deficiency (AATD) is caused by a single mutation in the SERPINA1 gene, leading to the accumulation of misfolded alpha-1 antitrypsin (ZAAT) in hepatocytes, which is associated with mitochondrial dysfunction. Research has shown that ZAAT aggregation in hepatocytes results in abnormal mitochondrial morphology and function, disrupting lipid metabolism balance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Nutrition & Dietetics
Veena Sangkhae, Allison L. Fisher, Tomas Ganz, Elizabeta Nemeth
Summary: During pregnancy, iron requirements increase significantly to support maternal and fetal development. While iron supplementation is common, excessive intake can also lead to adverse outcomes, especially in high-income countries where iron fortification and red meat consumption are prevalent.
ANNUAL REVIEW OF NUTRITION
(2023)
Review
Microscopy
Tiara V. Hinton, Sharon Batelu, Noah Gleason, Timothy L. Stemmler
Summary: Fe-S clusters play crucial roles in biochemical pathways in living organisms, synthesizing through mitochondrial and cytosolic pathways in eukaryotes. Deficiency in Fe-S clusters can be detrimental to cell and organism viability.
Article
Cell Biology
Hilmi Burak Kandilci, Gul Simsek, Tugba Zirapli, Mustafa Celebier
Summary: Iron deficiency is closely associated with mitochondrial dysfunction in heart failure patients. Iron plays a role as a structural component in mitochondria and also as a cofactor for the degradation of hypoxia inducible factor. This study used HL-1 cells to investigate the effects of iron depletion on mitochondrial function and reveal the mechanisms leading to cardiac failure.
Article
Biochemistry & Molecular Biology
Manman Xu, Yinghui Li, Dapeng Meng, Danyang Zhang, Bingjing Wang, Junxia Xie, Jun Wang
Summary: The role of microglia in iron metabolism and selective iron deposition in the substantia nigra pars compacta (SNpc) of Parkinson's disease (PD) brain is still unclear. This study found that 6-hydroxydopamine (6-OHDA) treatment induced the expression of divalent metal transporter-1 (DMT1) and iron influx in BV2 microglia cells and activated the microglia, leading to increased release of pro-inflammatory cytokines. Iron overloading suppressed the expression of iron regulatory protein 1 (IRP1), downregulating DMT1 and upregulating ferroportin 1 (FPN1) in microglial cells. The findings suggest that abnormal iron sequestration in microglia and activation of microglia may contribute to the pathological mechanisms in PD.
Review
Nutrition & Dietetics
Hana Manceau, Jerome Ausseil, Damien Masson, Jean-Paul Feugeas, Bernard Sablonniere, Regis Guieu, Herve Puy, Katell Peoc'h
Summary: Iron deficiency is a significant comorbidity of heart failure, often leading to rehospitalizations and reduced survival rates, however, correction with iron supplementation can improve functional capacity and quality of life in patients.
Article
Gastroenterology & Hepatology
Camille Danne, Chloe Michaudel, Jurate Skerniskyte, Julien Planchais, Aurelie Magniez, Allison Agus, Marie-Laure Michel, Bruno Lamas, Gregory Da Costa, Madeleine Spatz, Cyriane Oeuvray, Chloe Galbert, Maxime Poirier, Yazhou Wang, Alexia Lapiere, Nathalie Rolhion, Tatiana Ledent, Cedric Pionneau, Solenne Chardonnet, Floriant Bellvert, Edern Cahoreau, Amandine Rocher, Rafael Rose Arguello, Carole Peyssonnaux, Sabine Louis, Mathias L. Richard, Philippe Langella, Jamel El-Benna, Benoit Marteyn, Harry Sokol
Summary: Inflammatory bowel disease (IBD) is caused by a combination of genetic predisposition, gut microbiota dysbiosis, and environmental factors. Caspase recruitment domain 9 (Card9) is an IBD susceptibility gene that has been shown to protect against intestinal inflammation and fungal infection. However, the specific cell types and mechanisms involved in the CARD9 protective role against inflammation are still unknown.
Review
Medicine, General & Internal
Yasmeen Daou, Marion Falabregue, Charareh Pourzand, Carole Peyssonnaux, Marvin Edeas
Summary: This article discusses the impact of extracellular vesicles (EVs) on iron metabolism and homeostasis, as well as the role of gut microbiota in iron homeostasis, suggesting that EVs play a crucial role in the complex iron metabolism process.
FRONTIERS IN MEDICINE
(2022)
Article
Medical Laboratory Technology
Alexandre Raynor, Carmen Stefanescu, Arnaud Bruneel, Herve Puy, Katell Peoc'h, Hana Manceau
Summary: We present the case of a 42-year-old woman with chronic enteropathy and acquired atransferrinemia. Despite the absence of detectable serum transferrin, the patient only exhibited mild anaemia, and her haemoglobin concentration remained stable throughout the two-month hospitalization. The acquired atransferrinemia was believed to be secondary to chronic undernutrition, inflammation, and liver failure.
Article
Clinical Neurology
Arnaud Jacquier, Julian Theuriet, Fanny Fontaine, Valentine Mosbach, Nicolas Lacoste, Shams Ribault, Valerie Risson, Julien Carras, Laurent Coudert, Thomas Simonet, Philippe Latour, Tanya Stojkovic, Juliette Piard, Anne Cosson, Gaetan Lesca, Francoise Bouhour, Stephane Allouche, Helene Puccio, Antoine Pegat, Laurent Schaeffer
Summary: Jacquier et al. identified a homozygous variant in the COQ7 gene in a family with distal hereditary motor neuropathy. This variant leads to a decrease in coenzyme Q10 production, causing impaired mitochondrial metabolism. Coenzyme Q10 supplementation may serve as a potential treatment for this disorder.
Article
Biochemistry & Molecular Biology
Claudio Asencio, Thomas Schwarzl, Sudeep Sahadevan, Matthias W. Hentze
Summary: Small noncoding RNAs play important roles in cellular and organismal biology, working with RNA-binding proteins (RBPs). In order to specifically identify RBPs binding to small noncoding RNAs, a method called small noncoding RNA interactome capture (snRIC(2C)) was developed. Through this method, nearly 300 proteins that specifically bind to RNAs smaller than 200 nt in length (snRBPs) were identified, revealing differences from the total RNA-binding proteome. Further analysis showed that most glycolytic enzymes from yeast are snRBPs, and tRNA engagement of the glycolytic enzyme GAPDH is carbon source-dependent and regulated by the RNA polymerase III repressor Maf1, suggesting a regulatory interaction between glycolysis and RNA polymerase III activity. This study demonstrates the effectiveness of snRIC(2C) and other 2C-derived methods in studying RBPs and uncovering previously unrecognized interactions.
Article
Clinical Neurology
Ioannis Manolaras, Andrea Del Bondio, Olivier Griso, Laurence Reutenauer, Aurelie Eisenmann, Bianca H. Habermann, Helene Puccio
Summary: Manolaras et al. demonstrate that COQ8A-ataxia is primarily caused by mitochondrial dysfunction leading to calcium dysregulation in Purkinje neurons of the cerebellum. These abnormalities can be rescued in vitro by treatment with coenzyme Q10. It is a rare form of neurodegenerative disorder due to mutations in the COQ8A gene. The loss of COQ8A in Purkinje neurons is the main cause of cerebellar ataxia, resulting in abnormal dendritic arborizations, altered mitochondria function, and intracellular calcium dysregulation. Furthermore, they show that oxidative phosphorylation, particularly Complex IV, is primarily altered at presymptomatic stages of the disease, and CoQ10 treatment could rescue the pathology.
Article
Multidisciplinary Sciences
Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Sudeep Sahadevan, Frank Stein, Mandy Rettel, Bruno Galy, Matthias W. Hentze
Summary: The eRIC method was used to characterize the RNA-bound proteomes of three different mouse organs, revealing over 1300 active RNA-binding proteins, with nearly a quarter being previously unknown. Systematic differences in RNA binding were also observed between organs and cultured cells.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Bruno Galy, Marcus Conrad, Martina Muckenthaler
Summary: This review discusses the importance of iron in cellular functions and its tightly regulated mechanisms in mammals. Cells acquire, traffick, and export iron through various sensory and regulatory systems, and interact with systemic iron homeostasis control through multiple pathways. This knowledge is crucial for preventing diseases related to iron mismanagement.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Oncology
Maximiliano Gelli, Christophe Desterke, Mohamed Amine Bani, Valerie Boige, Charles Ferte, Peggy Dartigues, Bastien Job, Geraldine Perkins, Pierre Laurent-Puig, Diane Goere, Jacques R. R. Mathieu, Jerome Cartry, Michel Ducreux, Fanny Jaulin
Summary: This study aims to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes in colorectal cancer (CRC). By analyzing the transcriptomic mRNA sequencing, gene set enrichment analyses and immunohistochemistry of primary tumor specimens, we identified a 61-gene signature that distinguishes between liver and peritoneal metastatic routes. The application of this transcriptomic signature could potentially identify new therapeutic targets for stage IV CRC and contribute to individualized follow-up programs in stage II-III CRC.
Article
Cardiac & Cardiovascular Systems
Eshita Varma, Jana Burghaus, Thomas Schwarzl, Thileepan Sekaran, Parul Gupta, Agnieszka A. Gorska, Christoph Hofmann, Claudia Stroh, Lonny Juergensen, Verena Kamuf-Schenk, Xue Li, Rebekka Medert, Florian Leuschner, Vivien Kmietczyk, Marc Freichel, Hugo A. Katus, Matthias W. Hentze, Norbert Frey, Mirko Voelkers
Summary: RNA-protein interactions are important for cardiac function, but the regulation of individual RNA-binding proteins through signaling cascades during heart failure development is not well understood. The study found that mTOR signaling is linked to the upregulation of the RNA-binding protein Ybx1, which is involved in cardiac hypertrophy by regulating protein synthesis. The depletion of Ybx1 preserved heart function during pathological cardiac hypertrophy.
BASIC RESEARCH IN CARDIOLOGY
(2023)
Article
Neurosciences
Danique Beijer, Brent Fogel, Sergi Beltran, Matt Danzi, Andrea Nemeth, Stephan Zuchner, Matthis Synofzik
Summary: The Ataxia Global Initiative (AGI) is a global research platform aiming to enhance trial-readiness in degenerative ataxias. The AGI NGS working group focuses on improving methods for ataxia NGS analysis and data sharing to increase the number of genetically diagnosed ataxia patients. Collaboration between AGI and other research platforms has led to the diagnosis of over 500 ataxia patients and the discovery of more than 30 novel ataxia genes. The AGI NGS working group presents consensus recommendations for NGS data sharing initiatives, emphasizing harmonized variant analysis and standardized clinical and metadata collection.
Article
Biochemical Research Methods
Sudeep Sahadevan, Thileepan Sekaran, Nadia Ashaf, Marko Fritz, Matthias W. Hentze, Wolfgang Huber, Thomas Schwarzl
Summary: Transcriptome-wide detection of binding sites of RNA-binding proteins can be achieved using Individual-nucleotide crosslinking and immunoprecipitation (iCLIP) and its derivative enhanced CLIP (eCLIP) sequencing methods. The python package htseq-clip is introduced for preprocessing, extracting, and summarizing crosslink site counts from i/eCLIP experimental data. The package provides crosslink site count matrices and other metrics for filtering and downstream analyses, such as the identification of differential binding sites.
Article
Biochemistry & Molecular Biology
Thomas Schwarzl, Sudeep Sahadevan, Benjamin Lang, Milad Miladi, Rolf Backofen, Wolfgang Huber, Matthias W. Hentze, Gian Gaetano Tartaglia
Summary: Enhanced crosslinking and immunoprecipitation sequencing (eCLIP-seq) is a method for detecting RNA-binding protein binding sites. However, current analysis strategies have low replication and high false positive rates. DEWSeq, a R/Bioconductor package, improves the detection of binding regions by utilizing replicate information and size-matched input controls. It has been shown to significantly increase the number and quality of binding sites.
NUCLEIC ACIDS RESEARCH
(2023)
