Mitochondrial amino acid transporters can be subdivided on the basis of their substrates. Mitochondrial ornithine transporters play a role in the urea cycle by exchanging cytosolic ornithine (L-ornithine and D-ornithine) for mitochondrial citrulline (L-citrulline and D-citrulline) in equimolar amounts. Further members of the family include transporters of S-adenosylmethionine and carnitine.

Both ornithine transporters are inhibited by the polyamine spermine [3]. Loss-of-function mutations in these genes are associated with hyperornithinemia-hyperammonemia-homocitrullinuria.

* Key recommended reading is highlighted with an asterisk

* Fiermonte G, Dolce V, David L, Santorelli FM, Dionisi-Vici C, Palmieri F, Walker JE. (2003) The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem, 278 (35): 32778-83. [PMID:12807890]

* Fiermonte G, Palmieri L, Todisco S, Agrimi G, Palmieri F, Walker JE. (2002) Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem, 277 (22): 19289-94. [PMID:11897791]

* Hewton KG, Johal AS, Parker SJ. (2021) Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism. Metabolites, 11 (2). [PMID:33669382]

* Palmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrústegui J et al.. (2001) Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J, 20 (18): 5060-9. [PMID:11566871]

* Porcelli V, Fiermonte G, Longo A, Palmieri F. (2014) The human gene SLC25A29, of solute carrier family 25, encodes a mitochondrial transporter of basic amino acids. J Biol Chem, 289 (19): 13374-84. [PMID:24652292]

* Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White PJ, McGarrah RW, Ilkayeva OR et al.. (2019) BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature, 572 (7771): 614-619. [PMID:31435015]

1. Camacho JA, Obie C, Biery B, Goodman BK, Hu CA, Almashanu S, Steel G, Casey R, Lambert M, Mitchell GA et al.. (1999) Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat Genet, 22 (2): 151-8. [PMID:10369256]

2. Fiermonte G, Dolce V, David L, Santorelli FM, Dionisi-Vici C, Palmieri F, Walker JE. (2003) The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J Biol Chem, 278 (35): 32778-83. [PMID:12807890]

3. Fiermonte G, Paradies E, Todisco S, Marobbio CM, Palmieri F. (2009) A novel member of solute carrier family 25 (SLC25A42) is a transporter of coenzyme A and adenosine 3',5'-diphosphate in human mitochondria. J Biol Chem, 284 (27): 18152-9. [PMID:19429682]

4. Huizing M, Iacobazzi V, Ijlst L, Savelkoul P, Ruitenbeek W, van den Heuvel L, Indiveri C, Smeitink J, Trijbels F, Wanders R et al.. (1997) Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am J Hum Genet, 61 (6): 1239-45. [PMID:9399886]

5. Huizing M, Wendel U, Ruitenbeek W, Iacobazzi V, IJlst L, Veenhuizen P, Savelkoul P, van den Heuvel LP, Smeitink JA, Wanders RJ et al.. (1998) Carnitine-acylcarnitine carrier deficiency: identification of the molecular defect in a patient. J Inherit Metab Dis, 21 (3): 262-7. [PMID:9686371]

6. Molinari F, Raas-Rothschild A, Rio M, Fiermonte G, Encha-Razavi F, Palmieri L, Palmieri F, Ben-Neriah Z, Kadhom N, Vekemans M et al.. (2005) Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am J Hum Genet, 76 (2): 334-9. [PMID:15592994]

7. Tavoulari S, Lacabanne D, Pereira GC, Thangaratnarajah C, King MS, He J, Chowdhury SR, Tilokani L, Palmer SM, Prudent J et al.. (2024) Distinct roles for the domains of the mitochondrial aspartate/glutamate carrier citrin in organellar localization and substrate transport. Mol Metab, 90: 102047. [PMID:39419476]

8. Tavoulari S, Lacabanne D, Thangaratnarajah C, Kunji ERS. (2022) Pathogenic variants of the mitochondrial aspartate/glutamate carrier causing citrin deficiency. Trends Endocrinol Metab, 33 (8): 539-553. [PMID:35725541]

9. Wibom R, Lasorsa FM, Töhönen V, Barbaro M, Sterky FH, Kucinski T, Naess K, Jonsson M, Pierri CL, Palmieri F et al.. (2009) AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med, 361 (5): 489-95. [PMID:19641205]