Adenine nucleotide translocase and OXPHOS assembly

Trono and colleagues (2014) reviewed work on mitochondria from durum wheat. They report that these mitochondria make ATP from added ADP and export it. Translocation is the rate-limiting step of ATP appearance outside the organelle, so the translocator can regulate the rate of ATP synthesis.¹ The same group reports that ADP/ATP exchange was fully inhibited by atractyloside. This finding strongly suggests that adenine nucleotide movement depends on the ADP/ATP carrier. It was observed in de-energized mitochondria in a high-KCl medium.² Parodi-Rullán and colleagues (2019) describe the same basic function: matrix ATP is traded for ADP from the intermembrane space.³

Parodi-Rullán and colleagues (2019) built on earlier work from their group suggesting that ANT can be involved in assembly of respiratory chain supercomplexes.⁴ They silenced ANT1, the main cardiac isoform, in H9c2 cardiomyoblasts. The knockdown reduced the mitochondrial membrane potential. It raised total cellular ATP and raised total reactive oxygen species, but not mitochondrial ones.⁵ They also report that individual complexes I to IV kept their enzymatic activity.⁵

Atlante and Valenti (2021) summarise data in which ANT is damaged in two phases as far as exchange is concerned. Reactive oxygen species cause the first damage and caspase action adds the second.⁶ They add that ANT damaged by ROS can still translocate nucleotides, but only after caspase action does it take part in opening the permeability transition pore.⁶ Rottenberg (2023) describes that pore as voltage-gated. Lowering the membrane potential activates it and raising the potential inhibits it.⁷

Rauch-Kroehnert and colleagues (2026) argue that ANT should be read as more than a carrier. They describe it as a multifunctional hub that stabilises energetic balance, inner membrane integrity and quality control.⁸ They also state that it integrates mitochondrial stress signals with cellular and systemic responses. The routes they name are redox state, nucleic acid release, innate immune pathways and intercellular communication through extracellular pathways.⁹