Tricarboxylate transport protein, mitochondrial

SLC25A1 encodes the tricarboxylate transport protein, a mitochondrial antiporter that mediates electroneutral exchange of citrate from the mitochondria to the cytosol in return for malate and other tricarboxylic acid cycle intermediates (UniProt: P53007). In the cytoplasm, exported citrate supports fatty acid and sterol synthesis, glycolytic regulation, protein acetylation, and other metabolic processes. The protein can also exchange citrate for isocitrate, phosphoenolpyruvate, and related compounds.

SLC25A1 is associated with two rare inherited neurological disorders: Combined D-2- and L-2-hydroxyglutaric aciduria (D2L2AD, autosomal recessive), a neonatal-onset metabolic encephalopathy with seizures and developmental failure, and congenital myasthenic syndrome type 23 (CMS23, autosomal recessive), characterized by neuromuscular transmission failure and muscle weakness (UniProt: P53007).

SLC25A1 is upregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls across multiple subcellular fractions revealed a mean log2 fold-change of +0.95, suggesting increased citrate export capacity in AD pathology (Chaparral AD proteomics). This elevation may reflect altered metabolic demands or compensatory responses in degenerating neurons.