ADP/ATP translocase 3

ADP/ATP translocase 3 (SLC25A6) is a mitochondrial carrier protein that mediates bidirectional exchange of adenine nucleotides across the inner mitochondrial membrane, importing ADP for ATP synthesis and exporting ATP to support cellular energy demands (UniProt: P12236). Beyond its primary antiporter function, it participates in mitochondrial uncoupling through proton transport activity and contributes to mitochondrial permeability transition pore regulation, thereby influencing both energy production and cell death pathways.

The protein is expressed in human mitochondria and functions as a master regulator of mitochondrial energy homeostasis by balancing ATP production against thermogenesis. Its proton transporter activity requires free fatty acids as cofactors and is inhibited by ADP:ATP antiporter activity, establishing a regulatory mechanism for mitochondrial function (UniProt: P12236).

In Alzheimer's disease, SLC25A6 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.70 (Chaparral AD proteomics). This elevation was observed in human post-mortem AD brain examined via TMT-labeled proteomics across subcellular fractions, suggesting altered mitochondrial bioenergetics may be relevant to AD pathology.