Mitochondrial ATP-Mg/phosphate carriers transport divalent inorganic cations in complex with ATP

J Bioenerg Biomembr. 2017 Oct;49(5):369-380. doi: 10.1007/s10863-017-9721-0. Epub 2017 Jul 10.

Abstract

The ATP-Mg/phosphate carriers (APCs) modulate the intramitochondrial adenine nucleotide pool size. In this study the concentration-dependent effects of Mg2+ and other divalent cations (Me2+) on the transport of [3H]ATP in liposomes reconstituted with purified human and Arabidopsis APCs (hAPCs and AtAPCs, respectively, including some lacking their N-terminal domains) have been investigated. The transport of Me2+ mediated by these proteins was also measured. In the presence of a low external concentration of [3H]ATP (12 μM) and increasing concentrations of Me2+, Mg2+ stimulated the activity (measured as initial transport rate of [3H]ATP) of hAPCs and decreased that of AtAPCs; Fe2+ and Zn2+ stimulated markedly hAPCs and moderately AtAPCs; Ca2+ and Mn2+ markedly AtAPCs and moderately hAPCs; and Cu2+ decreased the activity of both hAPCs and AtAPCs. All the Me2+-dependent effects correlated well with the amount of ATP-Me complex present. The transport of [14C]AMP, which has a much lower ability of complexation than ATP, was not affected by the presence of the Me2+ tested, except Cu2+. Furthermore, the transport of [3H]ATP catalyzed by the ATP/ADP carrier, which is known to transport only free ATP and ADP, was inhibited by all the Me2+ tested in an inverse relationship with the formation of the ATP-Me complex. Finally, direct measurements of Mg2+, Mn2+, Fe2+, Zn2+ and Cu2+ showed that they are cotransported with ATP by both hAPCs and AtAPCs. It is likely that in vivo APCs transport free ATP and ATP-Mg complex to different degrees, and probably trace amounts of other Me2+ in complex with ATP.

Keywords: ATP-Mg/phosphate carrier; Divalent cation transport; Membrane transport; Mitochondria; Mitochondrial carrier; Mitochondrial transporter.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Antiporters / metabolism*
  • Arabidopsis Proteins / metabolism
  • Biological Transport
  • Cations, Divalent / metabolism*
  • Humans
  • Kinetics
  • Metals, Heavy / metabolism
  • Mitochondrial Proteins / metabolism*

Substances

  • ATP-Mg-Pi carrier proteins, mitochondria
  • Antiporters
  • Arabidopsis Proteins
  • Cations, Divalent
  • Metals, Heavy
  • Mitochondrial Proteins
  • Adenosine Triphosphate