{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:52:06Z","timestamp":1789696326806,"version":"4.0.1"},"reference-count":130,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany)"},{"name":"State of Thuringia (Landesgraduiertenstipendium)"},{"name":"Friedrich-Schiller Universit\u00e4t Jena"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cellular and organismic copper (Cu) homeostasis is regulated by Cu transporters and Cu chaperones to ensure the controlled uptake, distribution and export of Cu ions. Many of these processes have been extensively investigated in mammalian cell culture, as well as in humans and in mammalian model organisms. Most of the human genes encoding proteins involved in Cu homeostasis have orthologs in the model organism, Caenorhabditis elegans (C. elegans). Starting with a compilation of human Cu proteins and their orthologs, this review presents an overview of Cu homeostasis in C. elegans, comparing it to the human system, thereby establishing the basis for an assessment of the suitability of C. elegans as a model to answer mechanistic questions relating to human Cu homeostasis.<\/jats:p>","DOI":"10.3390\/cells13090727","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T08:08:27Z","timestamp":1713859707000},"page":"727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Copper Homeostasis in the Model Organism C. elegans"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-3285","authenticated-orcid":false,"given":"Verena Alexia","family":"Ohse","sequence":"first","affiliation":[{"name":"Nutrigenomics Section, Institute of Nutritional Sciences, Friedrich-Schiller-Universit\u00e4t Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1261-8911","authenticated-orcid":false,"given":"Lars-Oliver","family":"Klotz","sequence":"additional","affiliation":[{"name":"Nutrigenomics Section, Institute of Nutritional Sciences, Friedrich-Schiller-Universit\u00e4t Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2009-254X","authenticated-orcid":false,"given":"Josephine","family":"Priebs","sequence":"additional","affiliation":[{"name":"Nutrigenomics Section, Institute of Nutritional Sciences, Friedrich-Schiller-Universit\u00e4t Jena, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R877","DOI":"10.1016\/j.cub.2011.09.040","article-title":"Copper: An essential metal in biology","volume":"21","author":"Festa","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.3109\/10408444.2015.1074159","article-title":"Free radicals and related reactive species as mediators of tissue injury and disease: Implications for Health","volume":"45","author":"Kehrer","year":"2015","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.abb.2007.04.015","article-title":"Stimulation of phosphoinositide 3-kinase\/Akt signaling by copper and zinc ions: Mechanisms and consequences","volume":"463","author":"Barthel","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1021\/ja00905a001","article-title":"Hard and soft acids and bases","volume":"85","author":"Pearson","year":"1963","journal-title":"J. Am. Chem. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e05849","DOI":"10.7554\/eLife.05849","article-title":"C. elegans outside the Petri dish","volume":"4","author":"Frezal","year":"2015","journal-title":"eLife"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1093\/genetics\/77.1.71","article-title":"The genetics of Caenorhabditis elegans","volume":"77","author":"Brenner","year":"1974","journal-title":"Genetics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd2031","article-title":"Finding function in novel targets: C. elegans as a model organism","volume":"5","author":"Kaletta","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1534\/genetics.118.301307","article-title":"OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes","volume":"210","author":"Kim","year":"2018","journal-title":"Genetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1039\/C6MT00202A","article-title":"Defining the human copper proteome and analysis of its expression variation in cancers","volume":"9","author":"Blockhuys","year":"2017","journal-title":"Metallomics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1016\/j.cell.2022.09.021","article-title":"Intestinal mucin is a chaperone of multivalent copper","volume":"185","author":"Reznik","year":"2022","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Philipp, T.M., Gernoth, L., Will, A., Schwarz, M., Ohse, V.A., Kipp, A.P., Steinbrenner, H., and Klotz, L.O. (2023). Selenium-binding protein 1 (SELENBP1) is a copper-dependent thiol oxidase. Redox Biol., 65.","DOI":"10.1016\/j.redox.2023.102807"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1074\/jbc.RA117.000265","article-title":"The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis","volume":"293","author":"Boulet","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/iub.1618","article-title":"Copper metallothioneins","volume":"69","author":"Calvo","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00249-007-0234-3","article-title":"Copper binding to the Alzheimer\u2019s disease amyloid precursor protein","volume":"37","author":"Kong","year":"2008","journal-title":"Eur. Biophys. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vizan, P., Di Croce, L., and Aranda, S. (2021). Functional and Pathological Roles of AHCY. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.654344"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2206905119","DOI":"10.1073\/pnas.2206905119","article-title":"Memo1 binds reduced copper ions, interacts with copper chaperone Atox1, and protects against copper-mediated redox activity in vitro","volume":"119","author":"Zhang","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, X., Walke, G., and Wittung-Stafshede, P. (2023). Memo1 reduces copper-mediated reactive oxygen species in breast cancer cells. J. Inorg. Biochem., 247.","DOI":"10.1016\/j.jinorgbio.2023.112335"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1101\/gad.9.6.742","article-title":"MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions in Ras-mediated vulval induction and other developmental events","volume":"9","author":"Wu","year":"1995","journal-title":"Genes Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/biof.1836","article-title":"SEMO-1, a novel methanethiol oxidase in Caenorhabditis elegans, is a pro-aging factor conferring selective stress resistance","volume":"48","author":"Philipp","year":"2022","journal-title":"Biofactors"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41373","DOI":"10.1074\/jbc.M509142200","article-title":"Activation of CuZn superoxide dismutases from Caenorhabditis elegans does not require the copper chaperone CCS","volume":"280","author":"Jensen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hu, Y., Flockhart, I., Vinayagam, A., Bergwitz, C., Berger, B., Perrimon, N., and Mohr, S.E. (2011). An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-357"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/bioinformatics\/btn615","article-title":"AmiGO: Online access to ontology and annotation data","volume":"25","author":"Carbon","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10219","DOI":"10.1021\/es2027136","article-title":"Toxicity of ingested cadmium to the nematode Caenorhabditis elegans","volume":"45","author":"Schlottmann","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.chemosphere.2012.02.029","article-title":"Toxic and recovery effects of copper on Caenorhabditis elegans by various food-borne and water-borne pathways","volume":"87","author":"Yu","year":"2012","journal-title":"Chemosphere"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shafer, C.M., Tseng, A., Allard, P., and McEvoy, M.M. (2021). Strength of Cu-efflux response in Escherichia coli coordinates metal resistance in Caenorhabditis elegans and contributes to the severity of environmental toxicity. J. Biol. Chem., 297.","DOI":"10.1016\/j.jbc.2021.101060"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1038\/s41598-020-62560-4","article-title":"Copper(II)-binding equilibria in human blood","volume":"10","author":"Kirsipuu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/genetics\/159.1.133","article-title":"Genetic analysis of endocytosis in Caenorhabditis elegans: Coelomocyte uptake defective mutants","volume":"159","author":"Fares","year":"2001","journal-title":"Genetics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ydbio.2004.12.022","article-title":"Cyclin D involvement demarcates a late transition in C. elegans embryogenesis","volume":"279","author":"Yanowitz","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1897\/02-565","article-title":"The effects of metals and food availability on the behavior of Caenorhabditis elegans","volume":"22","author":"Boyd","year":"2003","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1242\/jcs.065433","article-title":"Molecular characterization of numr-1 and numr-2: Genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans","volume":"123","author":"Tvermoes","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1021\/es050154k","article-title":"Evidence for biogenic pyromorphite formation by the nematode Caenorhabditis elegans","volume":"39","author":"Jackson","year":"2005","journal-title":"Environ. Sci. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kar, S., Sen, S., Maji, S., Saraf, D., Paul, R., Dutt, S., Mondal, B., Rodriguez-Boulan, E., and Schreiner, R. (2022). Copper(II) import and reduction are dependent on His-Met clusters in the extracellular amino terminus of human copper transporter-1. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101631"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1182\/blood-2006-02-003681","article-title":"The Steap proteins are metalloreductases","volume":"108","author":"Ohgami","year":"2006","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10911","DOI":"10.1074\/jbc.RA118.003503","article-title":"CHCA-1 is a copper-regulated CTR1 homolog required for normal development, copper accumulation, and copper-sensing behavior in Caenorhabditis elegans","volume":"293","author":"Yuan","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0014-5793(98)01431-8","article-title":"Identification of the copper chaperone, CUC-1, in Caenorhabditis elegans: Tissue specific co-expression with the copper transporting ATPase, CUA-1","volume":"440","author":"Wakabayashi","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10534-020-00239-z","article-title":"The Caenorhabditis elegans homolog of human copper chaperone Atox1, CUC-1, aids in distal tip cell migration","volume":"33","author":"Zhang","year":"2020","journal-title":"BioMetals"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/jbc.M116.760876","article-title":"The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans","volume":"292","author":"Chun","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/toxsci\/kfn180","article-title":"Knock down of Caenorhabditis elegans cutc-1 exacerbates the sensitivity toward high levels of copper","volume":"106","author":"Calafato","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2018.07.020","article-title":"DMT1 and iron transport","volume":"133","author":"Yanatori","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C1525","DOI":"10.1152\/ajpcell.00480.2002","article-title":"DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells","volume":"284","author":"Arredondo","year":"2003","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"30485","DOI":"10.1074\/jbc.M112.364208","article-title":"Substrate Profile and Metal-ion Selectivity of Human Divalent Metal-ion Transporter-1","volume":"287","author":"Illing","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1039\/c5mt00097a","article-title":"Copper uptake by DMT1: A compensatory mechanism for CTR1 deficiency in human umbilical vein endothelial cells","volume":"7","author":"Lin","year":"2015","journal-title":"Metallomics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Au, C., Benedetto, A., Anderson, J., Labrousse, A., Erikson, K., Ewbank, J.J., and Aschner, M. (2009). SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in C. elegans. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007792"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mashock, M.J., Zanon, T., Kappell, A.D., Petrella, L.N., Andersen, E.C., and Hristova, K.R. (2016). Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167613"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nchembio.72","article-title":"Mechanisms for copper acquisition, distribution and regulation","volume":"4","author":"Kim","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hatori, Y., and Lutsenko, S. (2016). The Role of Copper Chaperone Atox1 in Coupling Redox Homeostasis to Intracellular Copper Distribution. Antioxidants, 5.","DOI":"10.3390\/antiox5030025"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.abb.2007.04.021","article-title":"Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in copper homeostasis","volume":"463","author":"Mercer","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"jcs261258","DOI":"10.1242\/jcs.261258","article-title":"Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B","volume":"137","author":"Ruturaj","year":"2024","journal-title":"J. Cell Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/oxfordjournals.jbchem.a021711","article-title":"Caenorhabditis elegans cDNA for a Menkes\/Wilson Disease Gene Homologue and Its Function in a Yeast CCC2 Gene Deletion Mutant","volume":"121","author":"Sambongi","year":"1997","journal-title":"J. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e12920","DOI":"10.1111\/tra.12920","article-title":"A new Caenorhabditis elegans model to study copper toxicity in Wilson disease","volume":"25","author":"Catalano","year":"2024","journal-title":"Traffic"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38084","DOI":"10.1074\/jbc.M105296200","article-title":"A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage","volume":"276","author":"Sturtz","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2430","DOI":"10.1038\/ncomms3430","article-title":"Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria","volume":"4","author":"Suzuki","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1016\/S0021-9258(18)63504-5","article-title":"Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein)","volume":"244","author":"McCord","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0022-2836(82)90174-7","article-title":"Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase","volume":"160","author":"Tainer","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1101\/gad.504808","article-title":"Against the oxidative damage theory of aging: Superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans","volume":"22","author":"Doonan","year":"2008","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.redox.2016.12.020","article-title":"Caenorhabditis elegans as a model for understanding ROS function in physiology and disease","volume":"11","author":"Veal","year":"2017","journal-title":"Redox Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5655","DOI":"10.1038\/ncomms6655","article-title":"Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans","volume":"6","author":"Guo","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105287","DOI":"10.1016\/j.isci.2022.105287","article-title":"Positive interaction between ASH and ASK sensory neurons accelerates nociception and inhibits behavioral adaptation","volume":"25","author":"Wu","year":"2022","journal-title":"iScience"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Boyd, S.D., Ullrich, M.S., Skopp, A., and Winkler, D.D. (2020). Copper Sources for Sod1 Activation. Antioxidants, 9.","DOI":"10.3390\/antiox9060500"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.1038\/s41598-020-60953-z","article-title":"Human glutaredoxin-1 can transfer copper to isolated metal binding domains of the P(1B)-type ATPase, ATP7B","volume":"10","author":"Maghool","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ferguson, G.D., and Bridge, W.J. (2019). The glutathione system and the related thiol network in Caenorhabditis elegans. Redox Biol., 24.","DOI":"10.1016\/j.redox.2019.101171"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ogata, F.T., Branco, V., Vale, F.F., and Coppo, L. (2021). Glutaredoxin: Discovery, redox defense and much more. Redox Biol., 43.","DOI":"10.1016\/j.redox.2021.101975"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"28052","DOI":"10.1074\/jbc.M304296200","article-title":"Factors controlling the uptake of yeast copper\/zinc superoxide dismutase into mitochondria","volume":"278","author":"Field","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.biocel.2018.07.001","article-title":"Mitochondrial copper homeostasis and its derailment in Wilson disease","volume":"102","author":"Zischka","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e64690","DOI":"10.7554\/eLife.64690","article-title":"Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes","volume":"10","author":"Zhu","year":"2021","journal-title":"eLife"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ruiz, L.M., Libedinsky, A., and Elorza, A.A. (2021). Role of Copper on Mitochondrial Function and Metabolism. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.711227"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Weishaupt, A.K., Lamann, K., Tallarek, E., Pezacki, A.T., Matier, C.D., Schwerdtle, T., Aschner, M., Chang, C.J., St\u00fcrzenbaum, S.R., and Bornhorst, J. (2024). Dysfunction in atox-1 and ceruloplasmin alters labile Cu levels and consequently Cu homeostasis in C. elegans. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1354627"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4207","DOI":"10.1128\/jb.177.15.4207-4215.1995","article-title":"Identification of cutC and cutF (nlpE) genes involved in copper tolerance in Escherichia coli","volume":"177","author":"Gupta","year":"1995","journal-title":"J. Bacteriol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbrc.2005.09.029","article-title":"Identification and characterization of a novel Cut family cDNA that encodes human copper transporter protein CutC","volume":"337","author":"Li","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jsb.2009.10.012","article-title":"Crystal structure of human copper homeostasis protein CutC reveals a potential copper-binding site","volume":"169","author":"Li","year":"2010","journal-title":"J. Struct. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12011-015-0577-z","article-title":"Silencing of Human CutC Gene (hCutC) Induces Apoptosis in HepG2 Cells","volume":"172","author":"Kunjunni","year":"2016","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1039\/C3MT00258F","article-title":"Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function","volume":"6","author":"Leong","year":"2014","journal-title":"Metallomics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e19493","DOI":"10.7554\/eLife.19493","article-title":"NADPH oxidase-mediated redox signaling promotes oxidative stress resistance and longevity through memo-1 in C. elegans","volume":"6","author":"Ewald","year":"2017","journal-title":"eLife"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s00775-011-0826-3","article-title":"Nematode and snail metallothioneins","volume":"16","author":"Dallinger","year":"2011","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"141021","DOI":"10.1016\/j.chemosphere.2023.141021","article-title":"Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins","volume":"350","author":"Essig","year":"2024","journal-title":"Chemosphere"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cmet.2011.12.003","article-title":"Lysosome-Related Organelles in Intestinal Cells Are a Zinc Storage Site in C. elegans","volume":"15","author":"Roh","year":"2012","journal-title":"Cell Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14594","DOI":"10.1021\/acs.chemrev.1c00371","article-title":"The Bioinorganic Chemistry of Mammalian Metallothioneins","volume":"121","author":"Krezel","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.21037\/atm.2019.03.18","article-title":"Clinical management of Wilson disease","volume":"7","author":"Hedera","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.bbamcr.2012.01.005","article-title":"The taste of heavy metals: Gene regulation by MTF-1","volume":"1823","author":"Lindert","year":"2012","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.jmb.2004.06.050","article-title":"C. elegans Metallothioneins: New Insights into the Phenotypic Effects of Cadmium Toxicosis","volume":"341","author":"Swain","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1016\/S0021-9258(18)53810-2","article-title":"The novel metallothionein genes of Caenorhabditis elegans. Structural organization and inducible, cell-specific expression","volume":"268","author":"Freedman","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"131324","DOI":"10.1016\/j.chemosphere.2021.131324","article-title":"Trans-generational effects of copper on nerve damage in Caenorhabditis elegans","volume":"284","author":"Zhang","year":"2021","journal-title":"Chemosphere"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7040","DOI":"10.1111\/j.1742-4658.2009.07417.x","article-title":"Caenorhabditis elegans metallothionein isoform specificity\u2014Metal binding abilities and the role of histidine in CeMT1 and CeMT2","volume":"276","author":"Bofill","year":"2009","journal-title":"FEBS J."},{"key":"ref_86","first-page":"186","article-title":"The function of metallothionein in Caenorhabditis elegans: Is detoxification of copper or of cadmium more important?","volume":"23","author":"Ibiam","year":"2015","journal-title":"Middle-East J. Sci. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1002\/etc.5620190823","article-title":"Transgenic strains of the nematode Caenorhabditis elegans as biomonitors of metal contamination","volume":"19","author":"Cioci","year":"2000","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1897\/08-496.1","article-title":"A transgenic strain of the nematode Caenorhabditis elegans as a biomonitor for heavy metal contamination","volume":"28","author":"Ma","year":"2009","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1016\/S0021-9258(18)83589-X","article-title":"The role of glutathione in copper metabolism and toxicity","volume":"264","author":"Freedman","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"11030","DOI":"10.1016\/S0021-9258(19)38552-7","article-title":"Reconstitution of Cu,Zn-superoxide dismutase by the Cu(I).glutathione complex","volume":"265","author":"Ciriolo","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0014-5793(93)81560-M","article-title":"An X-ray absorption study of the reconstitution process of bovine Cu,Zn superoxide dismutase by Cu(I)-glutathione complex","volume":"322","author":"Ascone","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/jnc.13567","article-title":"Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency","volume":"137","author":"Mercer","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.redox.2016.12.003","article-title":"Non-linear impact of glutathione depletion on C. elegans life span and stress resistance","volume":"11","author":"Urban","year":"2017","journal-title":"Redox Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1046\/j.1432-1327.2001.02293.x","article-title":"Caenorhabditis elegans expresses a functional phytochelatin synthase","volume":"268","author":"Clemens","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"20817","DOI":"10.1074\/jbc.C100152200","article-title":"A new pathway for heavy metal detoxification in animals. Phytochelatin synthase is required for cadmium tolerance in Caenorhabditis elegans","volume":"276","author":"Vatamaniuk","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0167-7799(01)01873-X","article-title":"Worms take the \u2018phyto\u2019 out of \u2018phytochelatins\u2019","volume":"20","author":"Vatamaniuk","year":"2002","journal-title":"Trends Biotechnol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Schwartz, M.S., Benci, J.L., Selote, D.S., Sharma, A.K., Chen, A.G., Dang, H., Fares, H., and Vatamaniuk, O.K. (2010). Detoxification of multiple heavy metals by a half-molecule ABC transporter, HMT-1, and coelomocytes of Caenorhabditis elegans. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009564"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1021\/pr9001806","article-title":"The metabolomic responses of Caenorhabditis elegans to cadmium are largely independent of metallothionein status, but dominated by changes in cystathionine and phytochelatins","volume":"8","author":"Hughes","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"885","DOI":"10.3389\/fphys.2018.00885","article-title":"N-Terminal Extension and C-Terminal Domains Are Required for ABCB6\/HMT-1 Protein Interactions, Function in Cadmium Detoxification, and Localization to the Endosomal-Recycling System in Caenorhabditis elegans","volume":"9","author":"Kim","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1039\/C6MT00176A","article-title":"Copper trafficking to the secretory pathway","volume":"8","author":"Lutsenko","year":"2016","journal-title":"Metallomics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.sbi.2019.05.002","article-title":"Copper trafficking in eukaryotic systems: Current knowledge from experimental and computational efforts","volume":"58","author":"Magistrato","year":"2019","journal-title":"Curr. Opin Struct. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"8544","DOI":"10.1021\/acs.inorgchem.5b01162","article-title":"Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the N-Terminus of Human Copper Transporter 1","volume":"54","author":"Pushie","year":"2015","journal-title":"Inorg. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9134","DOI":"10.1039\/c3cc45360j","article-title":"Kinetics and thermodynamics of metal binding to the N-terminus of a human copper transporter, hCTR1","volume":"49","author":"Du","year":"2013","journal-title":"Chem. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s00775-010-0663-9","article-title":"Methionine motifs of copper transport proteins provide general and flexible thioether-only binding sites for Cu(I) and Ag(I)","volume":"15","author":"Rubino","year":"2010","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12013-012-9358-x","article-title":"An all-atom model of the structure of human copper transporter 1","volume":"63","author":"Tsigelny","year":"2012","journal-title":"Cell Biochem. Biophys."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"18035","DOI":"10.1074\/jbc.M112.442426","article-title":"Rate and regulation of copper transport by human copper transporter 1 (hCTR1)","volume":"288","author":"Maryon","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.bpj.2015.11.016","article-title":"The C-Terminus of Human Copper Importer Ctr1 Acts as a Binding Site and Transfers Copper to Atox1","volume":"110","author":"Kahra","year":"2016","journal-title":"Biophys. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"26678","DOI":"10.1074\/jbc.M112.381178","article-title":"Functional partnership of the copper export machinery and glutathione balance in human cells","volume":"287","author":"Hatori","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"16371","DOI":"10.1021\/ja9058266","article-title":"Lysine-60 in copper chaperone Atox1 plays an essential role in adduct formation with a target Wilson disease domain","volume":"131","author":"Hussain","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1039\/c3mt00190c","article-title":"Conserved residue modulates copper-binding properties through structural dynamics in human copper chaperone Atox1","volume":"5","author":"Xi","year":"2013","journal-title":"Metallomics"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"13046","DOI":"10.1021\/bi0487591","article-title":"Solution structure of the apo and copper(I)-loaded human metallochaperone HAH1","volume":"43","author":"Anastassopoulou","year":"2004","journal-title":"Biochemistry"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s10534-017-0058-2","article-title":"The six metal binding domains in human copper transporter, ATP7B: Molecular biophysics and disease-causing mutations","volume":"30","author":"Li","year":"2017","journal-title":"Biometals"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5729","DOI":"10.1073\/pnas.0504472103","article-title":"Structure of human Wilson protein domains 5 and 6 and their interplay with domain 4 and the copper chaperone HAH1 in copper uptake","volume":"103","author":"Achila","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8468","DOI":"10.1021\/bi1008535","article-title":"NMR characterization of copper-binding domains 4-6 of ATP7B","volume":"49","author":"Fatemi","year":"2010","journal-title":"Biochemistry"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1021\/jp911208z","article-title":"Copper-transfer mechanism from the human chaperone Atox1 to a metal-binding domain of Wilson disease protein","volume":"114","author":"Crespo","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"112417","DOI":"10.1016\/j.celrep.2023.112417","article-title":"Structures of the human Wilson disease copper transporter ATP7B","volume":"42","author":"Yang","year":"2023","journal-title":"Cell Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1039\/C4MT00020J","article-title":"Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG\/2GSH and the availability of Cu(I)","volume":"6","author":"Brose","year":"2014","journal-title":"Metallomics"},{"key":"ref_119","first-page":"5297342","article-title":"Integrating Transcriptomics and Free Fatty Acid Profiling Analysis Reveal Cu Induces Shortened Lifespan and Increased Fat Accumulation and Oxidative Damage in C. elegans","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1006\/abbi.2001.2559","article-title":"Copper ions strongly activate the phosphoinositide-3-kinase\/Akt pathway independent of the generation of reactive oxygen species","volume":"397","author":"Ostrakhovitch","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.abb.2006.08.016","article-title":"Modulation of FoxO signaling in human hepatoma cells by exposure to copper or zinc ions","volume":"454","author":"Walter","year":"2006","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.abb.2014.06.004","article-title":"Insulin-like modulation of Akt\/FoxO signaling by copper ions is independent of insulin receptor","volume":"558","author":"Hamann","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Shomer, N., Kadhim, A.Z., Grants, J.M., Cheng, X., Alhusari, D., Bhanshali, F., Poon, A.F., Lee, M.Y.Y., Muhuri, A., and Park, J.I. (2019). Mediator subunit MDT-15\/MED15 and Nuclear Receptor HIZR-1\/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans. PLoS Genet., 15.","DOI":"10.1101\/565739"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"K\u00f6hnlein, K., Urban, N., Guerrero-G\u00f3mez, D., Steinbrenner, H., Urb\u00e1nek, P., Priebs, J., Koch, P., Kaether, C., Miranda-Vizuete, A., and Klotz, L.O. (2020). A Caenorhabditis elegans ortholog of human selenium-binding protein 1 is a pro-aging factor protecting against selenite toxicity. Redox Biol., 28.","DOI":"10.1016\/j.redox.2019.101323"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41588-017-0006-7","article-title":"Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis","volume":"50","author":"Pol","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Philipp, T.M., Will, A., Richter, H., Winterhalter, P.R., Pohnert, G., Steinbrenner, H., and Klotz, L.O. (2021). A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes. Redox Biol., 43.","DOI":"10.1016\/j.redox.2021.101972"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.redox.2016.12.035","article-title":"Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress","volume":"11","author":"Sies","year":"2017","journal-title":"Redox Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1021\/acs.chemrev.7b00205","article-title":"Chemical Biology of H2S Signaling through Persulfidation","volume":"118","author":"Filipovic","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/2665978601666200212105825","article-title":"Selenite-induced expression of a Caenorhabditis elegans pro-aging factor and ortholog of human selenium-binding protein 1","volume":"1","author":"Urban","year":"2020","journal-title":"Curr. Nutraceuticals"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00267-019-01234-y","article-title":"Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper","volume":"65","author":"Taylor","year":"2020","journal-title":"Environ. Manag."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/9\/727\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:32:35Z","timestamp":1760106755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/9\/727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":130,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["cells13090727"],"URL":"https:\/\/doi.org\/10.3390\/cells13090727","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]}}}