Peroxisomes are small organelles found in all eukaryotes, involved in a number of important metabolic pathways, including fatty acid α- and β-oxidation, biosynthesis of ether phospholipids and bile acids, and the degradation of purines, amino acids and polyamines. The functional role of the peroxisomal membrane as a permeability barrier to substrates and cofactors has been controversial for many years. The essential cofactors CoA, FAD and NAD+ are synthesized outside the peroxisomes and must be transported into the peroxisomal matrix where they are required for important processes. SLC25A17 (solute carrier family 25 member 17) is the only member of the mitochondrial carrier family that has 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. Moreover 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 [1]. The plant homologue of SLC25A17 is the peroxisomal protein PXN encoded by the Arabidopsis gene At2g39970 which has recently been found to transport NAD+, NADH, AMP and ADP [2]. Upon heterologous expression of PXN in bacteria followed by purification and reconstitution in liposomes, uptake and efflux experiments revealed that PXN transports coenzyme A (CoA), dephospho-CoA, acetyl-CoA and adenosine 3', 5'-phosphate (PAP), besides NAD+, NADH, AMP and ADP. PXN catalyzed fast counter-exchange of substrates and much slower uniport. Transport was saturable with a submillimolar affinity for NAD+, CoA and other substrates. The physiological role of PXN is probably to provide the peroxisomes with the essential coenzymes NAD+ and CoA [3]. [1] G. Agrimi, A. Russo, P. Scarcia, F. Palmieri, The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+, Biochem. J., 443 (2012) 241–247.

Human and plant peroxisomal cofactor transporters.

AGRIMI, GENNARO;SCARCIA, PASQUALE;PIERRI, CIRO LEONARDO;
2012-01-01

Abstract

Peroxisomes are small organelles found in all eukaryotes, involved in a number of important metabolic pathways, including fatty acid α- and β-oxidation, biosynthesis of ether phospholipids and bile acids, and the degradation of purines, amino acids and polyamines. The functional role of the peroxisomal membrane as a permeability barrier to substrates and cofactors has been controversial for many years. The essential cofactors CoA, FAD and NAD+ are synthesized outside the peroxisomes and must be transported into the peroxisomal matrix where they are required for important processes. SLC25A17 (solute carrier family 25 member 17) is the only member of the mitochondrial carrier family that has 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. Moreover 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 [1]. The plant homologue of SLC25A17 is the peroxisomal protein PXN encoded by the Arabidopsis gene At2g39970 which has recently been found to transport NAD+, NADH, AMP and ADP [2]. Upon heterologous expression of PXN in bacteria followed by purification and reconstitution in liposomes, uptake and efflux experiments revealed that PXN transports coenzyme A (CoA), dephospho-CoA, acetyl-CoA and adenosine 3', 5'-phosphate (PAP), besides NAD+, NADH, AMP and ADP. PXN catalyzed fast counter-exchange of substrates and much slower uniport. Transport was saturable with a submillimolar affinity for NAD+, CoA and other substrates. The physiological role of PXN is probably to provide the peroxisomes with the essential coenzymes NAD+ and CoA [3]. [1] G. Agrimi, A. Russo, P. Scarcia, F. Palmieri, The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+, Biochem. J., 443 (2012) 241–247.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/137649
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