Praseodymium trivalent ion is an effective inhibitor of mitochondrial basic amino acids and carnitine/acylcarnitine carriers.

We herein report the identification of the lantanide praseodymium trivalent ion Pr as inhibitor of mitochondrial transporters for basic amino acids and phylogenetically related carriers belonging to the Slc25 family. The inhibitory effect of Pr has been tested using mitochondrial transporters reconstituted into liposomes being effective in the micromolar range, acting as a competitive inhibitor of the human basic amino acids carrier (BAC, Slc25A29), the human carnitine/acylcarnitine carrier (CAC, Slc25A20). Furthermore, we provide computational evidence that the complete inhibition of the transport activity of the recombinant proteins is due to the Pr coordination to key acidic residues of the matrix salt bridge network. Besides being used as a first choice stop inhibitor for functional studies in vitro of mitochondrial carriers reconstituted in proteoliposomes, Pr might also represent a useful tool for structural studies of the mitochondrial carrier family.