Article
Chemistry, Inorganic & Nuclear
Nihar Ranjan Prusty, Francesca Camponeschi, Simone Ciofi-Baffoni, Lucia Banci
Summary: Iron-sulfur (Fe-S) clusters are versatile cofactors in biology, with the biogenesis of Fe-S proteins in the cytosol assisted by the cytosolic Fe-S protein assembly machinery, which includes proteins such as human ORAOV1 and YAE1. Structural and cluster binding studies showed that ORAOV1 and the YAE1-ORAOV1 complex can bind a [4Fe-4S](2+) cluster, suggesting their potential role in Fe-S cluster insertion into ABCE1.
INORGANICA CHIMICA ACTA
(2021)
Review
Biochemistry & Molecular Biology
Michael S. Petronek, Douglas R. Spitz, Bryan G. Allen
Summary: Cancer cells have a higher demand for iron due to their differential need for Fe-S biogenesis, which promotes cell growth and genomic stability. Researchers suggest that targeting Fe-S biogenesis through redox manipulation, Fe chelation, and Fe mimicry could be potential therapeutic strategies for cancer treatment.
Review
Chemistry, Inorganic & Nuclear
Jason C. Crack, Nick E. Le Brun
Summary: Iron-sulfur (FeS) clusters are protein cofactors essential for various biological functions such as electron transfer, catalysis, and gene regulation. Recent progress in using mass spectrometry has provided new insights into FeS cluster assembly and chemistry, particularly in transcriptional regulators coordinating cellular responses to changing conditions.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Yi Tong Vincent Aw, Azadeh Seidi, Jenni A. Hayward, Jiwon Lee, F. Victor Makota, Melanie Rug, Giel G. van Dooren
Summary: Fe-S clusters are essential for the survival of eukaryotes, with independent biosynthesis pathways occurring in different compartments of the cell. Little is known about cytosolic Fe-S cluster biosynthesis in apicomplexan parasites, but it has been found that NBP35 in Toxoplasma gondii localizes to the outer mitochondrial membrane and is critical for parasite proliferation.
MOLECULAR MICROBIOLOGY
(2021)
Article
Cell Biology
Arthavan Selvanathan, Bindu Parayil Sankaran
Summary: Iron-sulfur clusters (ISCs) are highly conserved moieties found in crucial proteins in bacteria, plants and mammals, with defects in the ISC pathway being associated with various human disease states. These disorders often involve neurological phenotypes and share common biochemical features. Therapies are primarily supportive, but improved understanding of the pathophysiology may lead to disease-modifying therapies in the future.
Review
Biochemistry & Molecular Biology
Francesca Camponeschi, Mario Piccioli, Lucia Banci
Summary: Despite limited knowledge about the mechanism of mitoNEET protein, its link to cancer suggests that targeting mitoNEET and its Fe-S clusters could inhibit cancer cell proliferation. Spectroscopic techniques, such as NMR, have been used to study mitoNEET and understand the differences in cluster stability and reactivity, as well as its cellular function. NMR assignment and characterization of the first coordination sphere can aid in drug design to interfere with cellular processes or participate in redox reactions or protein-protein recognition mechanisms.
Review
Biochemistry & Molecular Biology
Evan A. Talib, Caryn E. Outten
Summary: This review discusses the roles of CGFS glutaredoxins and BolA proteins in the synthesis and trafficking of Fe-S clusters, highlighting their shared and distinct functions in cluster biogenesis, storage, and signaling to transcriptional factors controlling iron metabolism in bacteria, fungi, humans, and plants.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Plant Sciences
Bing Yang, Chenyun Xu, Yuting Cheng, Ting Jia, Xueyun Hu
Summary: Iron-sulfur (Fe-S) clusters are ancient protein cofactors that exist ubiquitously in organisms and play important roles in various life processes. Plastids, semi-autonomous organelles believed to originate from cyanobacterial endosymbionts, have a Fe-S cluster biosynthesis and delivery pathway similar to cyanobacteria. Fe-S clusters are crucial for the normal functioning of downstream Fe-S proteins in plastids. Recent research has made significant progress in understanding this pathway and this review summarizes these findings as well as the remaining scientific challenges.
PLANT CELL REPORTS
(2023)
Review
Chemistry, Inorganic & Nuclear
Simone Ciofi-Baffoni, Claudia Andreini
Summary: Iron-sulfur clusters are protein cofactors that are crucial for cellular functions. CIAPIN1 proteins, which bind to iron-sulfur clusters, are involved in electron transfer pathways and cell death regulation. This study investigates the occurrence of CIAPIN1 proteins in different organisms and discusses their function and the role of Fe/S clusters.
Article
Biochemistry & Molecular Biology
Beatrice Bargagna, Lucia Banci, Francesca Camponeschi
Summary: Multiple mitochondrial dysfunctions syndrome type 2 with hyperglycinemia (MMDS2) is a severe disorder caused by biallelic mutations in the BOLA3 gene, resulting in impaired function of mitochondrial respiratory complexes and lipoic acid-dependent enzymes. The p.His96Arg mutation in BOLA3 leads to the formation of a non-functional heterocomplex with GLRX5, preventing the assembly of a [4Fe-4S] cluster on NFU1. These findings help explain the severe phenotype observed in MMDS2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jing Du, Zhaoyang Huang, Yanchun Li, Xueying Ren, Chaoting Zhou, Ruolan Liu, Ping Zhang, Guojie Lei, Jianxin Lyu, Jianghui Li, Guoqiang Tan
Summary: Copper is a necessary mineral nutrient but excess copper is cytotoxic. Wilson's disease is an autosomal recessive hereditary disease characterized by pathological copper accumulation in organs. The molecular mechanism of Wilson's disease is not fully understood and further research is needed to develop therapeutic strategies.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Oscar A. Campos, Narsis Attar, Chen Cheng, Maria Vogelauer, Nathan Mallipeddi, Stefan Schmollinger, Nedas Matulionis, Heather R. Christofk, Sabeeha S. Merchant, Siavash K. Kurdistani
Summary: This study reveals that histone H3-mediated Cu1+ toxicity is a major determinant of cellular functional pool of Fe-S clusters. Inadequate Fe-S cluster supply causes severe metabolic and growth defects. Decreasing Cu1+ abundance restores Fe-S cluster-dependent metabolism and growth.
Review
Chemistry, Multidisciplinary
Matthew J. Chalkley, Samuel I. Mann, William F. DeGrado
Summary: De novo protein design aims to define an amino acid sequence that encodes a specific structure and function of metalloproteins. By exploring ligand geometries, redox potentials, and catalytic reactions, significant progress has been made in designing diverse functional metalloproteins. The use of xenobiological metals and principles from inorganic chemistry also contributes to deriving new-to-nature functions in proteins.
NATURE REVIEWS CHEMISTRY
(2022)
Article
Oncology
Sylvain Garciaz, Andrew A. Guirguis, Sebastian Muller, Fiona C. Brown, Yih-Chih Chan, Ali Motazediani, Caitlin L. Rowe, James A. Kuzich, Kah Lok Chan, Kevin Tran, Lorey Smith, Laura MacPherson, Brian Liddicoat, Enid Y. N. Lam, Tatiana Caneque, Marian L. Burr, Veronique Litalien, Giovanna Pomilio, Mathilde Poplineau, Estelle Duprez, Sarah-Jane Dawson, Georg Ramm, Andrew G. Cox, Kristin K. Brown, David C. S. Huang, Andrew H. Wei, Kate McArthur, Raphael Rodriguez, Mark A. Dawson
Summary: Ironomycin is a drug that disrupts mitochondrial metabolism and induces cell death in cancer cells by reducing mitochondrial iron load and activating BAX/BAK. It exhibits synergy with BH3 mimetics and overcomes venetoclax resistance in cancers such as acute myeloid leukemia.
Review
Chemistry, Multidisciplinary
Karl J. Koebke, Tyler B. J. Pinter, Winston C. Pitts, Vincent L. Pecoraro
Summary: This review highlights the progress and milestone achievements in the field of de novo metalloprotein design in the past decade, with a focus on heme binding proteins, catalytic sites, and electron transfer sites. The significant contributions to our understanding of these subfields or de novo metalloprotein design are categorized and discussed in the context of history and science. Suggestions for future research directions are also provided.
Article
Multidisciplinary Sciences
Nunziata Maio, Bernard A. P. Lafont, Debangsu Sil, Yan Li, J. Martin Bollinger, Carsten Krebs, Theodore C. Pierson, W. Marston Linehan, Tracey A. Rouault
Summary: Research has shown that the catalytic subunit nsp12 of the SARS-CoV-2 RdRp complex ligates two iron-sulfur metal cofactors which are essential for viral replication and interaction with the viral helicase. Oxidation of these clusters by TEMPOL inhibits RdRp activity and blocks SARS-CoV-2 replication in cell culture, indicating that these iron-sulfur clusters could be targeted for therapy of COVID-19.
Article
Hematology
Nunziata Maio, De-Liang Zhang, Manik C. Ghosh, Anshika Jain, Anna M. SantaMaria, Tracey A. Rouault
Summary: Humans and other vertebrates have evolved effective mechanisms to maintain iron balance through the regulation of iron concentration and utilization at the cellular and systemic levels, involving iron-regulatory hormone hepcidin and iron regulatory proteins.
SEMINARS IN HEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nunziata Maio, Tracey A. Rouault
Article
Biochemistry & Molecular Biology
Nunziata Maio, Tracey A. Rouault
Article
Multidisciplinary Sciences
Elodie Mailler, Carlos M. Guardia, Xiaofei Bai, Michal Jarnik, Chad D. Williamson, Yan Li, Nunziata Maio, Andy Golden, Juan S. Bonifacino
Summary: ATG9A is a transmembrane protein involved in lipid mobilization, essential for autophagosome expansion, mitochondrial fatty acid import, and beta-oxidation. Depletion of ATG9A inhibits autophagy, increases lipid droplet size/number, and blocks transfer of fatty acids to mitochondria. ATG9A localizes to vesicular-tubular clusters associated with TMEM41B and plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Christina A. Porras, Tracey A. Rouault
Summary: This review provides an overview of the role of iron homeostasis disruption in various neurological disorders, discussing the consequences of both iron accumulation and deficiency. It also examines the history of animal models and presents a comparison of patients with a newly discovered neurodegenerative disorder caused by mutations in iron regulatory protein 2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Nunziata Maio, Sara Cherry, David C. Schultz, Brett L. Hurst, W. Marston Linehan, Tracey A. Rouault
Summary: TEMPOL has been shown to inhibit the RNA-dependent RNA polymerase of SARS-CoV-2 and effectively block viral replication in the Syrian hamster model. These findings support the potential application of TEMPOL as a highly efficacious antiviral against COVID-19 in humans.
Article
Multidisciplinary Sciences
Wing-Hang Tong, Hayden Ollivierre, Audrey Noguchi, Manik C. Ghosh, Danielle A. Springer, Tracey A. Rouault
Summary: Cardiomyopathy is a primary cause of death in Friedreich ataxia patients with defective iron-sulfur cluster biogenesis. The mTOR and AKT signaling cascades play crucial roles in regulating cardiovascular growth and homeostasis, with mTOR and AKT hyperactivations possibly as part of the metabolic stress response to ISC deficiencies.
Article
Multidisciplinary Sciences
Erika M. Palmieri, Ronald Holewinski, Christopher L. McGinity, Ciro L. Pierri, Nunziata Maio, Jonathan M. Weiss, Vincenzo Tragni, Katrina M. Miranda, Tracey A. Rouault, Thorkell Andresson, David A. Wink, Daniel W. McVicar
Summary: Nitric oxide (NO) reprograms macrophage metabolism by targeting mitochondrial aconitase 2 and pyruvate dehydrogenase (PDH), and this study shows that lipoate is used to generate nitroxyl (HNO) in this process. Lipoate facilitates NO-mediated production of HNO, which forms irreversible modifications on proteins, including PDH E2-associated lipoate.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Nunziata Maio, Russell P. Saneto, Richard Steet, Marcio A. Sotero de Menezes, Cindy Skinner, Tracey A. Rouault
Summary: Altered brain iron homeostasis can contribute to neurodegeneration. Mutations in the IREB2 gene can cause a newly characterized type of early onset progressive neurodegenerative disease, impacting iron metabolism regulation.
BRAIN COMMUNICATIONS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Erika Palmieri, Ronald Holewinski, Nunziata Maio, Christopher McGinity, Ciro Pierri, Tracey Rouault, Thorkell Andresson, David Wink, Daniel McVicar
