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RETRACTED ARTICLE: Identification of a novel Na(+)-coupled Fe(3+)-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

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 mamm...

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Detalles Bibliográficos
Autores principales: Ogura, Jiro, Babu, Ellappan, Miyauchi, Seiji, Ramachandran, Sabarish, Nemeth, Elizebeta, Bhutia, Yangzom D., Ganapathy, Vadivel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802838/
https://www.ncbi.nlm.nih.gov/pubmed/29410496
http://dx.doi.org/10.1038/s41598-018-20620-w
Descripción
Sumario: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 Fe(3+) was added during uptake without pretreatment. Similarly, uptake of Fe(3+) was enhanced by citrate. The Fe(3+)-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 Fe(3+)-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.