Mitochondrial nucleotide and glycine carriers (SLC25A24 ATP-Mg/Pi, SLC25A36 pyrimidine nucleotide, SLC25A38 glycine)

Mitochondria must import nucleotides and amino-acid precursors that are needed inside the matrix for mtDNA/RNA synthesis and for biosynthetic pathways confined to the organelle. This module groups three SLC25 inner-membrane carriers that supply such precursors. SLC25A24 (APC1/SCaMC-1) is a Ca2+-regulated ATP-Mg/phosphate carrier that exchanges cytosolic Mg-ATP (or ADP) for matrix inorganic phosphate, adjusting the total matrix adenine-nucleotide pool in response to cytosolic calcium via its N-terminal EF-hand domain. SLC25A36 (PNC1) is the pyrimidine nucleotide carrier that transports pyrimidine (and, less well, purine) nucleotides across the inner membrane, maintaining the mitochondrial nucleotide pool for replication and transcription. SLC25A38 is the glycine carrier that imports glycine into the matrix, providing the substrate for the first, committed step of heme biosynthesis (ALA synthase: glycine + succinyl-CoA -> 5-aminolevulinate) in erythroid cells, as well as for mitochondrial glycine/one-carbon metabolism. Loss-of-function causes precursor-specific disease: SLC25A24 — Fontaine progeroid syndrome (Gorlin-Chaudhry-Moss); SLC25A38 — autosomal-recessive congenital sideroblastic anemia.