ANT1 - ADP/ATP Translocase 1 - SLC25A4

Overview:

ATP is synthesized from oxidative phosphorylation in the mitochondrial matrix. However, it is required in the cytoplasm, where it can be used as the principal energy currency of the cell to power thermodynamically unfavorable reactions. After the consequent hydrolysis of ATP into ADP, ADP is required in the mitochondrial matrix, where it can be rephosphorylated to ATP. ANT1 transports the free, i.e. deprotonated, non-Magnesium, non-Calcium bound forms of ADP and ATP, in a 1:1 ratio across the mitochondrial inner membrane. Transport is fully reversible, and its directionality is governed by the concentrations of its substrates (ADP and ATP inside and outside mitochondria). ANT1 is the major ANT transporter in human cells and the archetypal protein of this family.

Data Sheet:

Gene:
SLC25A4

Human Protein:
UniProt: P12235

Synonyms:
ADP/ATP translocase 1: ADP,ATP carrier protein 1; ADP,ATP carrier protein, heart/skeletal muscle isoform T1; Adenine nucleotide translocator 1; ANT 1; Solute carrier family 25 member 4

Expression:
Highest espression in the heart, skeletal muscle, brain

Topology:
ANT1 is three-fold symmetric and monomeric, with the translocation pathway for the substrate through the centre. It contains six transmembrane α-helices that form a barrel that results in a deep cone-shaped depression accessible from the outside where the substrate binds.

Interactions:
ARL2, ARL2BP, SLC25A4

Modulators:
carboxyatractyloside, bongkrek acid, atractyloside dipotassium salt

Pathology:
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2 (PEOA2); Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type (MTDPS12B); Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type (MTDPS12A): All Pathologies are caused by mutations of the ANT1 gene.

Function:
Free ADP is transported from the cytoplasm to the mitochondrial matrix, while ATP produced from oxidative phosphorylation is transported from the mitochondrial matrix to the cytoplasm, thus providing the cells with its main energy currency.

Assays:
SSM-based assays on the SURFE²R instrument family

Recommended Reviews:

• Clémençon et al.: The Mitochondrial ADP/ATP Carrier (SLC25 Family): Pathological Implications of Its Dysfunction (2013) Molecular Aspects of Medicine 34(2–3):485-493

Transporter classification database:

• 2.A.29.1.2 Mitochondrial ADP/ATP carrier 1 (AAC1); ADP/ATP translocase 1; adenine nucleotide translocator 1 (ANT1)

UniProt:

• ADP/ATP translocase 1 (SLC25A4, Homo sapiens)

IUPHAR/PBS:

• Mitochondrial nucleotide transporter subfamily