Calcium-dependent mitochondrial aspartate-glutamate carrier 2 (AGC2)

Aspartate-glutamate carrier 2 (AGC2), also known as citrin, is a calcium-dependent mitochondrial solute transporter encoded by the SLC25A13 gene (UniProt: Q96CQ1). It plays a critical role in the malate-aspartate shuttle, which facilitates the transfer of reducing equivalents from the cytosol to the mitochondria for oxidative phosphorylation (PubMed: 10441251). AGC2 is primarily expressed in the liver, heart, and kidneys, where it mediates the electrogenic exchange of mitochondrial aspartate for cytosolic glutamate and a proton (NCBI Gene: 10165). This transport process is essential for the urea cycle, gluconeogenesis, and protein synthesis. Mutations in the SLC25A13 gene lead to citrin deficiency, manifesting as neonatal intrahepatic cholestasis (NICCD) or adult-onset type II citrullinemia (CTLN2) (GeneReviews: NBK1181). While not a traditional target for inhibitory drugs, AGC2 is a focus for metabolic therapies and gene replacement strategies aimed at restoring transport function. Management typically involves dietary modifications, such as a low-carbohydrate, high-protein diet, and supplementation with arginine or sodium pyruvate to bypass metabolic blocks (PubMed: 31515104).

Other names

CitrinSolute carrier family 25 member 13SLC25A13Mitochondrial aspartate-glutamate carrier 2

Electrogenic exchange of mitochondrial aspartate for cytosolic glutamate plus a proton across the inner mitochondrial membrane, driven by the mitochondrial membrane potential.