Nonmitochondrial ATP/ADP transporters accept phosphate as third substrate.

Chlamydiales and Rickettsiales as metabolically impaired, intracellular pathogenic bacteria essentially rely on "energy parasitism" by the help of nucleotide transporters (NTTs). Also in plant plastids NTT-type carriers catalyze ATP/ADP exchange to fuel metabolic processes. The uptake of ATP4-, followed by energy consumption and the release of ADP3-, would lead to a metabolically disadvantageous accumulation of negative charges in form of inorganic phosphate (Pi) in the bacterium or organelle if no interacting Pi export system exists. We identified that Pi is a third substrate of several NTT-type ATP/ADP transporters. During adenine nucleotide hetero-exchange, Pi is cotransported with ADP in a one-to-one stoichiometry. Additionally, Pi can be transported in exchange with solely Pi. This Pi homo-exchange depends on the presence of ADP and provides a first indication for only one binding center involved in import and export. Furthermore, analyses of mutant proteins revealed that Pi interacts with the same amino acid residue as the gamma-phosphate of ATP. Import of ATP in exchange with ADP plus Pi is obviously an efficient way to couple energy provision with the export of the two metabolic products (ADP plus Pi) and to maintain cellular phosphate homeostasis in intracellular living "energy parasites" and plant plastids. The additional Pi transport capacity of NTT-type ATP/ADP transporters makes the existence of an interacting Pi exporter dispensable and might explain why a corresponding protein so far has not been identified.