InterPro domain: IPR044712

This entry represents a group of substrate carrier proteins that are related to the nicotinamide adenine dinucleotide transporter found in mitochondria, including human NAD/FAD transporter SLC25A32, yeast Yea6/Flx1/Yia6, and AtNDT1/AtNDT2/PXN/AtFOLT1 from Arabidopsis. Structurally, they consist of three tandem repeats of a domain of approximately one hundred residues. Each of these domains contains two transmembrane regions.

In budding yeasts, Yea6 and Yia6 are mitochondrial inner membrane carrier protein that mediates the import of NAD+ into mitochondria [ 1 , 2 ]. Flx1 transports FAD from the cytosol to the mitochondrial matrix [ 3 , 4 ].

In humans, SLC25A32 transports folate and FAD across the inner membranes of mitochondria [ 5 , 6 , 7 ]. Mutations in the SLC25A32 gene cause neural tube defects (NTD) [ 8 ]. SLC25A32 has also been implicated in multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II (GAII) [ 8 ].

In Arabidopsis, AtNDT1 and AtNDT2 are able to catalyze the import of NAD+ in mitochondria [ 8 ]. PXN (At2g39970) is a peroxisomal NAD carrier that is able to catalyze NAD, NADH, AMP, ADP, adenosine 3', 5'-phosphate (PAP) and CoA transport. It supplies the peroxisomes with NAD by importing this coenzyme from the cytosol in exchange with AMP [ 9 ]. AtFOLT1 (At5g66380) has been shown to mediate folate import into chloroplast [ 10 ].

1. SLC25A51 is a mammalian mitochondrial NAD⁺ transporter. Nature 588, 1524-31
2. Identification of the mitochondrial NAD+ transporter in Saccharomyces cerevisiae. J Biol Chem 281, 95-102
3. FLX1 codes for a carrier protein involved in maintaining a proper balance of flavin nucleotides in yeast mitochondria. J Biol Chem 271
4. Riboflavin uptake and FAD synthesis in Saccharomyces cerevisiae mitochondria: involvement of the Flx1p carrier in FAD export. J Biol Chem 279, 7392-7
5. A mutation inactivating the mitochondrial inner membrane folate transporter creates a glycine requirement for survival of chinese hamster cells. J Biol Chem 279, 33829-36
6. Formate rescues neural tube defects caused by mutations in Slc25a32. Proc Natl Acad Sci U S A 115, 4690-4695
7. Identification of the human mitochondrial FAD transporter and its potential role in multiple acyl-CoA dehydrogenase deficiency. Mol Genet Metab 86, 441-7
8. Molecular identification and functional characterization of Arabidopsis thaliana mitochondrial and chloroplastic NAD+ carrier proteins. J Biol Chem 284, 31249-59
9. Metabolic Roles of Plant Mitochondrial Carriers. Biomolecules 10, 34823-31
10. Folate metabolism in plants: an Arabidopsis homolog of the mammalian mitochondrial folate transporter mediates folate import into chloroplasts. J Biol Chem 280, 174-179