title: Multidrug and toxic compound extrusion protein-1 (MATE1/SLC47A1) is a novel flavonoid transporter.
abstract: Dietary flavonoids have various biological functions. However, their cellular transport mechanisms are largely unknown. We have determined that the multidrug and toxic compound extrusion transporter-1 (MATE1) is a membrane transporter for flavonoids and has a high affinity for quercetin. HEK293T cells overexpressing MATE1 exhibited increased intracellular quercetin accumulation. This effect disappeared in the presence of a MATE1 inhibitor and after MATE1 gene knockdown. HepG2 cells expressed MATE1 significantly, with the uptake quercetin of which was dramatically reduced with MATE1 inhibition. On the basis of immunofluorescence analysis, MATE1 was highly expressed in peroxisomes and the endoplasmic reticulum (ER) as well as in plasma membranes in the liver and intestine, which suggests potential accumulation of quercetin in peroxisomes and the ER in these tissues. Fluorescent microscopic analysis confirmed selective accumulation of qurcetin in peroxisome. The effects of quercetin on cellular lipid reduction and glucose uptake were exaggerated with MATE1 overexpression. In conclusion, MATE1 is a membrane transporter for quercetin; its overexpression enhances the hypolipidemic activity of quercetin and cellular glucose transport. Considering the low bioavailability of quercetin, appropriate regulation of MATE1 expression may optimize cellular quercetin concentrations and promote health benefits.
authors.affiliation: Department of Biotechnology, BK21-PLUS Graduate School of Life Sciences and Biotechnology, Korea University , Seoul 136-713, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Yeojin
authors.initials: Y
authors.lastname: Kim
authors.forename: Hojoung
authors.initials: H
authors.lastname: Lee
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism / Q000493:pharmacokinetics*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D056945:Hep G2 Cells / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism; D011794:Quercetin / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D005419:Flavonoids; C514424:MATE1 protein, mouse; D027701:Organic Cation Transport Proteins; C521869:SLC47A1 protein, human; D011794:Quercetin
keywords: flavonoid transporter; lipid metabolism; multidrug and toxic compound extrusion transporter-1; quercetin