Regulation of iron transport and the role of transferrin

Gkouvatsos, Konstantinos; Papanikolaou, George; Pantopoulos, Kostas

doi:10.1016/j.bbagen.2011.10.013

Cited by 410 publications

(338 citation statements)

References 246 publications

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“…The resulting ferric iron could be loaded onto transferrin and transported to iron-deficient cells for uptake, as is the case in mammals (31). Alternatively, oxidation of ferrous iron followed by transferrin loading may play a protective role by limiting toxic radical formation, which is generated by ferrous but not ferric iron (1), or, it may have an immune function, given that ferric-transferrin is less likely than free iron to serve as a source of iron for pathogens (32).…”

Section: Mco1 Is Present On Basal Surface Of Digestive System and Malmentioning

confidence: 99%

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster

Lang

Braun

Kanost

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Multicopper ferroxidases catalyze the oxidation of ferrous iron to ferric iron. In yeast and algae, they participate in cellular uptake of iron; in mammals, they facilitate cellular efflux. The mechanisms of iron metabolism in insects are still poorly understood, and insect multicopper ferroxidases have not been identified. In this paper, we present evidence that Drosophila melanogaster multicopper oxidase-1 (MCO1) is a functional ferroxidase. We identified candidate iron-binding residues in the MCO1 sequence and found that purified recombinant MCO1 oxidizes ferrous iron. An association between MCO1 function and iron homeostasis was confirmed by two observations: RNAi-mediated knockdown of MCO1 resulted in decreased iron accumulation in midguts and whole insects, and weak knockdown increased the longevity of flies fed a toxic concentration of iron. Strong knockdown of MCO1 resulted in pupal lethality, indicating that MCO1 is an essential gene. Immunohistochemistry experiments demonstrated that MCO1 is located on the basal surfaces of the digestive system and Malpighian tubules. We propose that MCO1 oxidizes ferrous iron in the hemolymph and that the resulting ferric iron is bound by transferrin or melanotransferrin, leading to iron storage, iron withholding from pathogens, regulation of oxidative stress, and/or epithelial maturation. These proposed functions are distinct from those of other known ferroxidases. Given that MCO1 orthologues are present in all insect genomes analyzed to date, this discovery is an important step toward understanding iron metabolism in insects.

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Section: Mco1 Is Present On Basal Surface Of Digestive System and Malmentioning

confidence: 99%

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster

Lang

Braun

Kanost

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…(45,46). Es considerado el principal captador celular de hierro y se localiza en la membrana del enterocito, del hepatocito, de los eritrocitos, en la placenta, en la médula ósea y en el músculo esquelético (9,11,33,47,48).…”

Section: El Transportador 1 De Metales Divalentes (Dmt1)unclassified

“…La Tf es nuevamente secretada a la circulación y el TfR-1 se ancla en la membrana apical. La repetición de este ciclo permite captar más hierro y formar nuevos complejos (10,14,33).…”

Section: El Receptor 1 De Transferrina (Tfr1)unclassified

“…TfR2 al igual que el TfR1 es un receptor homodimérico transmembranal, encargado de importar hierro a las células; con un extremo corto N-terminal citosólico, un solo dominio transmembranal y un largo ectodominio C-terminal (47) (9,33,47,48). Sin embargo, el TfR2 tiene la capacidad de sensar los cambios de hierro en circulación, interactuar con la holotransferrina y activar la hepcidina; los mecanismos por los cuales se logra la interacción de estas proteínas aún se desconocen (48).…”

Section: El Receptor 2 De Transferrina (Tfr2)unclassified

“…En el TfR2 se ha descrito la mutación autosómica recesiva, denominada hemocromatosis hereditaria tipo 3, que se manifiesta clínicamente con una concentración elevada de hierro corporal, incremento en la saturación de Tf y de la Ft sérica (9,33,47). Proteína transmembrana HFE: la conforman 348 aa (49), con el extremo N terminal extracelular y el C terminal hacia el citosol; en el dominio extracelular, se encuentran los enlaces disulfuro que permiten la unión con microglobulinas (50).…”

Section: El Receptor 2 De Transferrina (Tfr2)unclassified

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Proteínas relacionadas con el metabolismo del hierro corporal

Corrales-Agudelo¹,

Sosa

Herrera

2017

Perspect Nutr Humana

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Como citar este artículo: Corrales-Agudelo V, Parra-Sosa BE, Burgos-Herrera LC. Proteínas relacionadas con el metabolismo del hierro corporal. Perspect Nutr Humana. 2016;18:95-116. DOI:10.17533/udea.penh.v18n1a08 Proteínas relacionadas con el metabolismo del hierro corporal ResumenAntecedentes: el hierro es uno de los minerales más estudiados; existe amplia información en cuanto a su metabolismo, función, interacciones y regulación; sin embargo, los estudios y análisis realizados se basan en proteínas específicas y pocos integran, en un solo texto, las características de estas moléculas relacionadas con el metabolismo del hierro corporal. Objetivo: profundizar en los aspectos moleculares, metabólicos y de modulación de las proteínas que participan en la homeostasis del hierro y en sus interacciones. Materiales y métodos: se hizo una búsqueda sistemática de información en bases de datos científicas de artículos sobre el tema, publicados entre 2006 y 2016. Resultados: la homeostasis del hierro corporal, es un proceso complejo y altamente regulado por diferentes moléculas que participan de manera integrada en su metabolismo; en los últimos años han surgido nuevas proteínas, algunas de ellas participan en el transporte de otros nutrientes y se les ha encontrado relación con el control humoral y celular del hierro; además, involucran la participación de varios órganos, tejidos y sistemas. Esta revisión incluye proteínas encargadas de facilitar el aprovechamiento biológico del nutriente, así como aquellas que protegen a las células de toxicidad por exceso de este mineral.Palabras clave: hierro, proteínas de unión al hierro, expresión génica, oxidación-reducción, homeostasis, deficiencia de hierro. Proteínas del metabolismo del hierro 96Vol. 18, N° 1, enero-junio de 2016Proteins associated with the metabolism of total body iron Abstract Background: Iron is an essential nutrient well studied for its role in human health, and much evidence exists regarding its metabolism, functions, interactions, and regulations. However, studies and analyses that have been done are often based on specific proteins and few integrate into a single text the characteristics of multiple proteins related to total body iron metabolism. Objective: Explore in-depth the molecular, metabolic, and modulation aspects of proteins that participate in iron homeostasis and related interactions. Materials and methods: A literature review was completed using scientific databases in conjunction with a search for related scientific articles published between 2006 and 2016. Results: Homeostasis of total body iron stores is a complex process that is highly regulated by various molecules that participate in an integrated manner in iron metabolism. In recent years, new proteins have been discovered regarding the humoral and cellular control of iron, some of which are also involved in the transport of other nutrients. Additionally, these proteins involve participation from various organs, tissues, and systems. This review includes proteins responsible for ...

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Photo‐release of Metal Ions in Living Cells

Gwizdala¹,

Burdette²

2014

Inorganic Chemical Biology

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Regulation of iron transport and the role of transferrin

Cited by 410 publications

References 246 publications

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster

Proteínas relacionadas con el metabolismo del hierro corporal

Photo‐release of Metal Ions in Living Cells

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