SLC25A1

SLC25A1 is a human gene that encodes the mitochondrial citrate carrier, also known as the citrate carrier (CIC). It is a member of the mitochondrial carrier family (SLC25) and localizes to the inner mitochondrial membrane. The protein functions as a transporter that exchanges citrate and other tricarboxylates with malate and related dicarboxylates across the membrane, facilitating the export of citrate from mitochondria to the cytosol.

Function and role in metabolism: By exporting citrate to the cytosol, SLC25A1 supplies acetyl-CoA for fatty acid and cholesterol synthesis via ATP citrate lyase. Cytosolic citrate also partially regulates glycolysis by inhibiting phosphofructokinase-1, linking mitochondrial energy status to biosynthetic pathways. The transporter’s activity thus connects mitochondrial energy production with cytosolic lipid synthesis and metabolic regulation. The protein has the typical structure of mitochondrial carriers, with six transmembrane helices and conserved sequence motifs across three repeats, and it is expressed in a variety of tissues, with notable levels in liver, adipose tissue, and brain.

Clinical significance: Pathogenic variants in SLC25A1 cause a rare congenital disorder termed SLC25A1 deficiency or combined dicarboxylate transporter deficiency (CDCD). The clinical spectrum is broad and often includes neonatal or early infancy seizures, hypotonia, developmental delay, microcephaly, and progressive brain abnormalities; metabolic features such as lactic acidosis may be present. Diagnosis relies on genetic testing and metabolic evaluation, and treatment is primarily supportive.

Genetics and research: SLC25A1 is conserved across eukaryotes and is a focus in studies of metabolic regulation, lipid synthesis, and neurodevelopment. In research contexts, modulation of citrate transport can influence cytosolic acetyl-CoA availability and cellular lipogenesis, with implications for metabolic disorders and cancer biology.