@entity1 equilibrative @entity2353 transporter-3 ( @entity23658 ) was recently reported as a pH-dependent, intracellular (lysosomal) transporter capable of transporting @entity778 ( @entity778 ) @entity20620 (ddNs). Because most anti- @entity778 ddNs (e.g., @entity9611 , @entity5647 ) exhibit clinical @entity2383 , we investigated whether @entity23658 facilitates transport of anti- @entity778 ddNs into the mitochondria. Cellular fractionation and immunofluorescence microscopy studies in several @entity1 cell lines identified a substantial presence of @entity23658 in the mitochondria, with additional presence at the cell surface of two placental cell lines (JAR, JEG3). Mitochondrial or cell surface @entity23658 expression was confirmed in @entity1 hepatocytes and placental tissues, respectively. Unlike endogenous @entity23658 , yellow fluorescent protein (YFP)-tagged @entity23658 was partially directed to the lysosomes. @entity1238 oocytes expressing @entity2733 -terminal-deleted @entity23658 (expressed at the cell surface) showed pH-dependent interaction with several classes of @entity2642 (anti- @entity778 ddNs, @entity136 , @entity64012 , @entity5371 ) that produce @entity2383 . Transport studies in @entity23658 gene-silenced JAR cells showed significant reduction in mitochondrial transport of @entity2642 and @entity2353 drugs. Our data suggest that cellular localization of @entity23658 is cell type dependent and the native transporter is substantially expressed in mitochondria and/or cell surface. @entity23658 -mediated mitochondrial transport may play an important role in mediating clinically observed @entity2383 of @entity2353 drugs. In addition, our finding that @entity23658 is a mitochondrial transporter is consistent with the recent finding that mutations in the @entity23658 gene cause an @entity74 in @entity1 called the H syndrome.

Facilitated mitochondrial import of antiviral and anticancer @entity2353 drugs by @entity1 equilibrative XXXX transporter-3.

@entity1 :: ('9606', 'Species') :: ['human', 'humans', 'Human'] @entity23658 :: ('55315', 'Gene') :: ['hENT3'] @entity778 :: ('MESH:D015658', 'Disease') :: ['anti-human immunodeficiency virus', 'HIV'] @entity2353 :: ('CHEBI:33838', 'Chemical') :: ['nucleoside'] @entity9611 :: ('MESH:D015215', 'Chemical') :: ['zidovudine'] @entity1238 :: ('8355', 'Species') :: ['Xenopus'] @entity2642 :: ('MESH:D009705', 'Chemical') :: ['nucleosides'] @entity64012 :: ('MESH:C043457', 'Chemical') :: ['fialuridine'] @entity2733 :: ('CHEBI:29345', 'Chemical') :: ['NH2'] @entity20620 :: ('MESH:D015224', 'Chemical') :: ['dideoxynucleosides'] @entity5647 :: ('CHEBI:10110', 'Chemical') :: ['AZT'] @entity74 :: ('MESH:D030342', 'Disease') :: ['autosomal recessive disorder'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine'] @entity5371 :: ('MESH:D012254', 'Chemical') :: ['ribavirin'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial toxicity']
@entity2353 :: (CHEBI:33838,Chemical) :: ['nucleoside']
