Figure 2. The two transport functions of ADP/ATP carrier (AAC).

(A) ADP/ATP exchange. Cytosolic Mg²⁺-free ADP binds to the c-state of AAC (the substrate binding site exposed to the cytosol) [1], AAC changes its conformation to the m-state (the substrate binding site exposed to the matrix), and ADP dissociates into the matrix [2]. AAC dwells in the m-state [3]. When matrix Mg²⁺-free ATP binds to the m-state [4], AAC changes its conformation to the c-state, and ATP dissociates into cytosol [5] (31). (B) The fatty acid (FA)-dependent H⁺ leak. When ADP and ATP are not associated with the AAC substrate binding site, cytosolic free long-chain FA can bind either to the c-state [1] or m-state [2] of AAC and activate H⁺ leak. Matrix long-chain FA cannot activate H⁺ leak via AAC in either of the two states (22).