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

Giovanna Incampo, Nicola Giangregorio, Nicola Gambacorta, Orazio Nicolotti, Concetta Pacifico, Luigi Palmieri, Annamaria Tonazzi

Biochimica et biophysica acta. Bioenergetics 2022 Jun 01

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We herein report the identification of the lantanide praseodymium trivalent ion Pr3+ as inhibitor of mitochondrial transporters for basic amino acids and phylogenetically related carriers belonging to the Slc25 family. The inhibitory effect of Pr3+ 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 Pr3+ 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, Pr3+ might also represent a useful tool for structural studies of the mitochondrial carrier family. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Giovanna Incampo, Nicola Giangregorio, Nicola Gambacorta, Orazio Nicolotti, Concetta Pacifico, Luigi Palmieri, Annamaria Tonazzi. Praseodymium trivalent ion is an effective inhibitor of mitochondrial basic amino acids and carnitine/acylcarnitine carriers. Biochimica et biophysica acta. Bioenergetics. 2022 Jun 01;1863(5):148557