RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

Abstract NaCT is a Na+-coupled transporter for citrate expressed in hepatocytes and neurons. It is the mammalian ortholog of INDY (I’m Not Dead Yet), a transporter which modifies lifespan in Drosophila. Here we describe a hitherto unknown transport system for citrate in mammalian cells. When liver a...

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Autores principales:	Jiro Ogura, Ellappan Babu, Seiji Miyauchi, Sabarish Ramachandran, Elizebeta Nemeth, Yangzom D. Bhutia, Vadivel Ganapathy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce0a9e30d5a64551b8dba0593afbfdc6
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spelling	oai:doaj.org-article:ce0a9e30d5a64551b8dba0593afbfdc62021-12-02T15:08:34ZRETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells10.1038/s41598-018-20620-w2045-2322https://doaj.org/article/ce0a9e30d5a64551b8dba0593afbfdc62018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20620-whttps://doaj.org/toc/2045-2322Abstract NaCT is a Na+-coupled transporter for citrate expressed in hepatocytes and neurons. It is the mammalian ortholog of INDY (I’m Not Dead Yet), a transporter which modifies lifespan in Drosophila. Here we describe a hitherto unknown transport system for citrate in mammalian cells. When liver and mammary epithelial cells were pretreated with the iron supplement ferric ammonium citrate (FAC), uptake of citrate increased >10-fold. Iron chelators abrogated the stimulation of citrate uptake in FAC-treated cells. The iron exporter ferroportin had no role in this process. The stimulation of citrate uptake also occurred when Fe3+ was added during uptake without pretreatment. Similarly, uptake of Fe3+ was enhanced by citrate. The Fe3+-citrate uptake was coupled to Na+. This transport system was detectable in primary hepatocytes and neuronal cell lines. The functional features of this citrate transport system distinguish it from NaCT. Loss-of-function mutations in NaCT cause early-onset epilepsy and encephalopathy; the newly discovered Na+-coupled Fe3+-citrate transport system might offer a novel treatment strategy for these patients to deliver citrate into affected neurons independent of NaCT. It also has implications to iron-overload conditions where circulating free iron increases, which would stimulate cellular uptake of citrate and consequently affect multiple metabolic pathways.Jiro OguraEllappan BabuSeiji MiyauchiSabarish RamachandranElizebeta NemethYangzom D. BhutiaVadivel GanapathyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiro Ogura Ellappan Babu Seiji Miyauchi Sabarish Ramachandran Elizebeta Nemeth Yangzom D. Bhutia Vadivel Ganapathy RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
description	Abstract NaCT is a Na+-coupled transporter for citrate expressed in hepatocytes and neurons. It is the mammalian ortholog of INDY (I’m Not Dead Yet), a transporter which modifies lifespan in Drosophila. Here we describe a hitherto unknown transport system for citrate in mammalian cells. When liver and mammary epithelial cells were pretreated with the iron supplement ferric ammonium citrate (FAC), uptake of citrate increased >10-fold. Iron chelators abrogated the stimulation of citrate uptake in FAC-treated cells. The iron exporter ferroportin had no role in this process. The stimulation of citrate uptake also occurred when Fe3+ was added during uptake without pretreatment. Similarly, uptake of Fe3+ was enhanced by citrate. The Fe3+-citrate uptake was coupled to Na+. This transport system was detectable in primary hepatocytes and neuronal cell lines. The functional features of this citrate transport system distinguish it from NaCT. Loss-of-function mutations in NaCT cause early-onset epilepsy and encephalopathy; the newly discovered Na+-coupled Fe3+-citrate transport system might offer a novel treatment strategy for these patients to deliver citrate into affected neurons independent of NaCT. It also has implications to iron-overload conditions where circulating free iron increases, which would stimulate cellular uptake of citrate and consequently affect multiple metabolic pathways.
format	article
author	Jiro Ogura Ellappan Babu Seiji Miyauchi Sabarish Ramachandran Elizebeta Nemeth Yangzom D. Bhutia Vadivel Ganapathy
author_facet	Jiro Ogura Ellappan Babu Seiji Miyauchi Sabarish Ramachandran Elizebeta Nemeth Yangzom D. Bhutia Vadivel Ganapathy
author_sort	Jiro Ogura
title	RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
title_short	RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
title_full	RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
title_fullStr	RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
title_full_unstemmed	RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells
title_sort	retracted article: identification of a novel na+-coupled fe3+-citrate transport system, distinct from mammalian indy, for uptake of citrate in mammalian cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ce0a9e30d5a64551b8dba0593afbfdc6
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RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

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