ADP/ATP translocase 1

ADP/ATP translocase 1 (SLC25A4) is a mitochondrial inner membrane protein that catalyzes the exchange of cytoplasmic ADP for matrix ATP, enabling oxidative phosphorylation and energy export to fuel cellular processes (UniProt: P12235). Beyond its primary antiporter function, it regulates mitochondrial thermogenesis via proton transport, modulates the mitochondrial permeability transition pore, and promotes mitophagy through interaction with TIMM44 (UniProt: P12235). The protein is expressed in tissues dependent on oxidative metabolism.

Pathogenic variants in SLC25A4 cause mitochondrial diseases including progressive external ophthalmoplegia (PEOA2) and mitochondrial DNA depletion syndromes (MTDPS12A/12B), characterized by myopathy, cardiomyopathy, and respiratory insufficiency (UniProt: P12235). These conditions reflect critical roles in ATP homeostasis and mitochondrial integrity.

In Alzheimer's Disease, SLC25A4 shows ambiguous regulation across subcellular fractions in post-mortem brain tissue with a mean log2 fold-change of 0.73 (Chaparral AD proteomics). This modest, inconsistent directionality across fractions suggests complex changes in mitochondrial energetics in AD neuropathology, warranting further investigation into AD-specific mitochondrial dysfunction.