Reactome | SLC25A12,13 exchange L-Glu and L-Asp

SLC25A12,13 exchange L-Glu and L-Asp

Stable Identifier

R-HSA-372448

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial inner membrane, mitochondrial matrix

Synonyms

H(+)(out) + L-aspartate(in) + L-glutamate(out) => H(+)(in) + L-aspartate(out) + L-glutamate(in), SLC25A12,13 exchange cytosolic L-Glu for mitochondrial matrix L-Asp, aspartate [mitochondrial matrix] + glutamate [cytosol] => aspartate [cytosol] + glutamate [mitochondrial matrix]

ReviewStatus

5/5

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Calcium-binding mitochondrial carrier proteins SLC25A12 (Aralar, AGC1) and SLC25A13 (Citrin, Aralar2, AGC2), located in the inner mitochondrial membrane, mediate the exchange of cytosolic aspartate and mitochondrial glutamate (Palmieri et al., 2001; González-Moreno et al., 2023). The exchange is physiologically irreversible because of the potential across the inner mitochondrial membrane (positive outside, negative inside). In the body, SLC25A12 is found mainly in the heart, skeletal muscle, and brain, while SCL25A13 is widely expressed but most abundant in the liver (del Arco et al., 2000; Palmieri et al., 2001). Mutations in SLC25A12 can cause a form of early-onset epileptic encephalopathy (DEE39, MIM:612949; Wibom et al., 2009; reviewed in Pardo et al., 2022). Defects in SLC25A13 are associated with type II citrullinemia, characterized by a liver-specific deficiency of the urea cycle enzyme argininosuccinate synthase (Kobayashi et al., 1999, Saheki et al., 2002; González-Moreno et al., 2023; reviewed in Hayasaka, 2021)

Literature References

PubMed ID	Title	Journal	Year
10369257	The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein Kobayashi, K, Scherer, SW, Kondo, I, Ikeda, S, Crackower, MA, Iijima, M, Boright, AP, Hirano, R, Lee, JR, Tsui, LC, Saheki, T, Begum, L, Sinasac, DS, Terazono, H, Yasuda, T	Nat Genet	1999
36967723	Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver Calvo, E, González-Moreno, L, Pérez-Carreras, M, Santamaría-Cano, A, Vázquez, J, Paradela, A, González-Aseguinolaza, G, Satrústegui, J, del Arco, A, Contreras, L, Saheki, T, Martín, MA, Martínez-Chantar, ML, García-Picazo, A	Mol Genet Metab Rep	2023
12602510	Pathogenesis and pathophysiology of citrin (a mitochondrial aspartate glutamate carrier) deficiency Kobayashi, K, Saheki, T, Begum, L, Iijima, M, Jalil, MA, Li, MX, Yasuda, T, Gao, HZ, Yamaguchi, N, Nishi, I	Metab Brain Dis	2002
19641205	AGC1 deficiency associated with global cerebral hypomyelination Wedell, A, Sterky, FH, Töhönen, V, Pierri, CL, Kucinski, T, Naess, K, Barbaro, M, Lasorsa, FM, Jonsson, M, Palmieri, F, Wibom, R	N Engl J Med	2009
10642534	Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues del Arco, A, Satrústegui, J, Agudo, M	Biochem J	2000
32740958	Metabolic basis and treatment of citrin deficiency Hayasaka, K	J Inherit Metab Dis	2021
11566871	Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria del Arco, A, Kobayashi, K, Saheki, T, Iijima, M, Walker, JE, Runswick, MJ, Lasorsa, FM, Palmieri, L, Palmieri, F, Pardo, B, Satrústegui, J	EMBO J	2001
35008954	AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease del Arco, A, Contreras, L, Herrada-Soler, E, Pardo, B, Satrústegui, J	Int J Mol Sci	2022