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

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dc.contributor.author Lang, Minglin
dc.contributor.author Braun, Caroline L.
dc.contributor.author Kanost, Michael R.
dc.contributor.author Gorman, Maureen J.
dc.date.accessioned 2012-11-12T17:54:16Z
dc.date.available 2012-11-12T17:54:16Z
dc.date.issued 2012-11-12
dc.identifier.uri http://hdl.handle.net/2097/14932
dc.description.abstract 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 orthologs are present in all insect genomes analyzed to date, this discovery is an important step toward understanding iron metabolism in insects. en_US
dc.language.iso en_US en_US
dc.relation.uri http://www.pnas.org/content/109/33/13337.full en_US
dc.subject Biological sciences en_US
dc.subject Genetics en_US
dc.subject Multicopper ferroxidases en_US
dc.subject Drosophila melanogaster en_US
dc.title Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster en_US
dc.type Article (author version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1073/pnas.1208703109 en_US
dc.citation.epage 13342 en_US
dc.citation.issue 33 en_US
dc.citation.jtitle Proceedings of the National Academy of Sciences of the United States of America en_US
dc.citation.spage 13337 en_US
dc.citation.volume 109 en_US
dc.contributor.authoreid langml en_US
dc.contributor.authoreid kanost en_US
dc.contributor.authoreid mgorman en_US

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