SLC25A4 Gene (ANT1): Function, Mutations & Associated Diseases | Biomedical Resource

The SLC25A4 gene encodes the adenine nucleotide translocator 1 (ANT1), a critical inner mitochondrial membrane protein. ANT1 is the most abundant mitochondrial protein and functions as a gated pore that exchanges cytosolic ADP for mitochondrial ATP, a rate-limiting step in oxidative phosphorylation. This exchange is essential for providing energy to the cell. Mutations in SLC25A4 are primarily associated with autosomal dominant progressive external ophthalmoplegia (PEO) with mitochondrial DNA deletions and autosomal recessive mitochondrial DNA depletion syndrome (MTDPS12), which can manifest as encephalopathy, cardiomyopathy, and myopathy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Oxidative phosphorylation (OXPHOS)

• Mitochondrial ADP/ATP transport

• Cardiac muscle contraction

• Skeletal muscle contraction

The SLC25A4 protein, also known as ANT1, is a 298-amino acid protein with six transmembrane domains. It forms a homodimer in the inner mitochondrial membrane. The protein undergoes a conformational change to alternately expose its substrate binding site to the intermembrane space (for ADP) and the matrix (for ATP). This strict antiport mechanism is driven by the membrane potential and is essential for cellular energy homeostasis. The protein also plays a role in the mitochondrial permeability transition pore (mPTP), a key player in cell death pathways. Structural studies have shown that the substrate is bound in a deep cavity, and the translocation involves a rocker-switch mechanism.