Nonmitochondrial ATP/ADP transporters accept phosphate as third substrate

Area of Science:

• Microbiology
• Cell Biology
• Biochemistry

Background:

• Intracellular bacteria like Chlamydiales and Rickettsiales, and plant plastids, are metabolically limited and depend on energy parasitism.
• Nucleotide transporters (NTTs) are crucial for exchanging ATP and ADP to meet energy demands in these systems.
• A potential issue is the accumulation of negatively charged inorganic phosphate (Pi) during ATP uptake and ADP release.

Purpose of the Study:

• To investigate the role of NTTs in phosphate transport.
• To determine if NTTs can directly facilitate inorganic phosphate (Pi) transport.
• To understand the mechanism of energy and phosphate homeostasis in intracellular bacteria and plastids.

Main Methods:

• Functional characterization of NTT-type transporters.
• Analysis of mutant NTT proteins to identify substrate interaction sites.
• Investigating substrate exchange mechanisms, including adenine nucleotides and inorganic phosphate.

Main Results:

• Inorganic phosphate (Pi) is identified as a third substrate for several NTT-type ATP/ADP transporters.
• Pi is cotransported with ADP during adenine nucleotide hetero-exchange in a 1:1 stoichiometry.
• Pi can also undergo homo-exchange, indicating a single binding site for import and export, and Pi interacts with the same residue as ATP's gamma-phosphate.

Conclusions:

• NTT-type transporters facilitate ATP import coupled with the export of ADP and Pi, maintaining cellular phosphate homeostasis.
• The dual function of NTTs in nucleotide and phosphate transport makes a separate Pi exporter unnecessary.
• This finding explains the absence of identified Pi exporter proteins in these systems.