Tricarboxylate transport protein, mitochondrial

The structure of the tricarboxylate transport protein is consistent with the structures of other mitochondrial carriers. The amino and carboxy termini are located on the cytosolic side of the inner mitochondrial membrane. The two α-helices of each repeated domain are connected by hydrophilic loops located on the matrix side of the membrane. A salt bridge network is present on both the matrix side and cytoplasmic side of the tricarboxylate transport protein. == Transport mechanism ==

The tricarboxylate transport protein exists in two states: a cytoplasmic state where it accepts malate from the cytoplasm and a matrix state where it accepts citrate from the mitochondrial matrix. A single binding site is present near the center of the cavity of the tricarboxylate transport protein, which can be either exposed to the cytosol or the mitochondrial matrix depending on the state. == Disease relevance ==

Mutations in this gene have been associated with the inborn error of metabolism combined D-2- and L-2-hydroxyglutaric aciduria, which was the first reported case of a pathogenic mutation of the SLC25A1 gene. Patients with D-2/L-2-hydroxyglutaric aciduria display neonatal onset metabolic encephalopathy, infantile epilepsy, global developmental delay, muscular hypotonia and early death. It is believed low levels of citrate in the cytosol and high levels of citrate in the mitochondria caused by the impaired citrate transport plays a role in the disease. and the production of inflammatory mediators. Therefore, it has been suggested that inhibition of the tricarboxylate transport protein may have a therapeutic effect in chronic inflammation diseases and cancer. == See also ==