The human SLC25A42 protein, ortholog of mitochondrial carrier Leu5p of S. cerevisiae, transports Coenzyme A and Adenosine 3’,5’-diphosphate G. Fiermonte, E. Paradies, S. Todisco, C.M.T. Marobbio, M.A Di Noia, and F. Palmieri Department of Pharmaco-Biology, Laboratory and Molecular Biology, University of Bari, Bari, Italy The essential cofactor Coenzyme A (CoA) is required in many intra-mitochondrial metabolic pathways. The CoA is synthesized outside the mitochondrial matrix, therefore must be transported into mitochondria. In S. cerevisiae, the mitochondrial carrier Leu5p is involved in the accumulation of CoA in the mitochondrial matrix. In fact, deletion of LEU5 (leu5) causes a reduction of mitochondrial coenzyme A (CoA) levels and growth defect on YP supplemented with glycerol or other non fermentative carbon sources. The closest relatives of Leu5p in human are SLC25A16 (37% identity) and SLC25A42 (31% identity). In this study we provide direct evidence that SLC25A42 is a novel transporter of CoA. SLC25A42 is localized in the mitochondrial inner membrane and is highly expressed in virtually all tissues. This protein was overexpressed in Escherichia coli, purified, reconstituted in phospholipid vesicles, and shown to transport CoA, dephospho-CoA, Adenosine 3’,5’-diphosphate (PAP), and (deoxy)adenine nucleotides with high specificity and by a counter-exchange mechanism. The expression of SLC25A42 protein in LEU5 cells fully restores the phenotype of the LEU5 strain, indicating that the main function of both proteins is probably to catalyze the entry of CoA into mitochondria in exchange for adenine nucleotides and PAP.

The human SLC25A42 protein, ortholog of mitochondrial carrier Leu5p of S. cerevisiae, transports Coenzyme A and Adenosine 3’, 5’- diphosphate

FIERMONTE, Giuseppe;TODISCO, SIMONA;MAROBBIO, CARLO MARYA;DI NOIA, MARIA ANTONIETTA;
2010-01-01

Abstract

The human SLC25A42 protein, ortholog of mitochondrial carrier Leu5p of S. cerevisiae, transports Coenzyme A and Adenosine 3’,5’-diphosphate G. Fiermonte, E. Paradies, S. Todisco, C.M.T. Marobbio, M.A Di Noia, and F. Palmieri Department of Pharmaco-Biology, Laboratory and Molecular Biology, University of Bari, Bari, Italy The essential cofactor Coenzyme A (CoA) is required in many intra-mitochondrial metabolic pathways. The CoA is synthesized outside the mitochondrial matrix, therefore must be transported into mitochondria. In S. cerevisiae, the mitochondrial carrier Leu5p is involved in the accumulation of CoA in the mitochondrial matrix. In fact, deletion of LEU5 (leu5) causes a reduction of mitochondrial coenzyme A (CoA) levels and growth defect on YP supplemented with glycerol or other non fermentative carbon sources. The closest relatives of Leu5p in human are SLC25A16 (37% identity) and SLC25A42 (31% identity). In this study we provide direct evidence that SLC25A42 is a novel transporter of CoA. SLC25A42 is localized in the mitochondrial inner membrane and is highly expressed in virtually all tissues. This protein was overexpressed in Escherichia coli, purified, reconstituted in phospholipid vesicles, and shown to transport CoA, dephospho-CoA, Adenosine 3’,5’-diphosphate (PAP), and (deoxy)adenine nucleotides with high specificity and by a counter-exchange mechanism. The expression of SLC25A42 protein in LEU5 cells fully restores the phenotype of the LEU5 strain, indicating that the main function of both proteins is probably to catalyze the entry of CoA into mitochondria in exchange for adenine nucleotides and PAP.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/34263
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