title: The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+.
abstract: The essential cofactors CoA, FAD and NAD+ are synthesized outside the peroxisomes and therefore must be transported into the peroxisomal matrix where they are required for important processes. In the present study we have functionally identified and characterized SLC25A17 (solute carrier family 25 member 17), which is the only member of the mitochondrial carrier family that has previously been shown to be localized in the peroxisomal membrane. Recombinant and purified SLC25A17 was reconstituted into liposomes. Its transport properties and kinetic parameters demonstrate that SLC25A17 is a transporter of CoA, FAD, FMN and AMP, and to a lesser extent of NAD+, PAP (adenosine 3',5'-diphosphate) and ADP. SLC25A17 functioned almost exclusively by a counter-exchange mechanism, was saturable and was inhibited by pyridoxal 5'-phosphate and other mitochondrial carrier inhibitors. It was expressed to various degrees in all of the human tissues examined. Its main function is probably to transport free CoA, FAD and NAD+ into peroxisomes in exchange for intraperoxisomally generated PAP, FMN and AMP. The present paper is the first report describing the identification and characterization of a transporter for multiple free cofactors in peroxisomes.
authors.affiliation: Department of Biosciences, Biotechnology and Pharmacological Sciences, University of Bari, 70125 Bari, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Agrimi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Russo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Scarcia
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Palmieri
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000249:Adenosine Monophosphate / Q000737:chemistry; D003065:Coenzyme A / Q000737:chemistry*; D004926:Escherichia coli; D005486:Flavin Mononucleotide / Q000737:chemistry; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D009243:NAD / Q000737:chemistry*; D009928:Organ Specificity; D020675:Peroxisomes / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification
chemical_list: D008081:Liposomes; D008565:Membrane Proteins; D011994:Recombinant Proteins; C116693:peroxisomal membrane protein 34; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D005486:Flavin Mononucleotide; C010840:adenosine 3'-phosphate-5'-phosphate; D003065:Coenzyme A