title: Intracellular dehydroascorbic acid inhibits SVCT2-dependent transport of ascorbic acid in mitochondria.
abstract: Exposure of U937 cells to low concentrations of L-ascorbic acid (AA) is associated with a prompt cellular uptake and a further mitochondrial accumulation of the vitamin. Under the same conditions, dehydroascorbic acid (DHA) uptake was followed by rapid reduction and accumulation of identical intracellular levels of AA, however, in the absence of significant mitochondrial uptake. This event was instead observed after exposure to remarkably greater concentrations of DHA. Furthermore, experiments performed in isolated mitochondria revealed that DHA transport through hexose transporters and Na(+) -dependent transport of AA were very similar. These results suggest that the different subcellular compartmentalization of the vitamin is mediated by events promoting inhibition of mitochondrial AA transport, possibly triggered by low levels of DHA. We obtained results in line with this notion in intact cells, and more direct evidence in isolated mitochondria. This inhibitory effect was promptly reversible after DHA removal and comparable with that mediated by established inhibitors, as quercetin. The results presented collectively indicate that low intracellular concentrations of DHA, because of its rapid reduction back to AA, are a poor substrate for direct mitochondrial uptake. DHA concentrations, however, appear sufficiently high to mediate inhibition of mitochondrial transport of AA/DHA-derived AA.
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Fiorani
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Azzolini
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guidarelli
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Cerioni
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Scotti
authors.affiliation: Dipartimento di Scienze Biomolecolari Università degli Studi di Urbino "Carlo Bo", 61029 Urbino, Italy. Electronic address: orazio.cantoni@uniurb.it.
authors.forename: Orazio
authors.initials: O
authors.lastname: Cantoni
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects*; D045744:Cell Line, Tumor; D003683:Dehydroascorbic Acid / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism*; D020298:U937 Cells
chemical_list: C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D012964:Sodium; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid
keywords: Ascorbic acid; Ascorbic acid transport; Dehydroascorbic acid; SVCT2