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The mitochondrial oxoglutarate carrier: from identification to mechanism

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An Erratum to this article was published on 07 November 2012

Abstract

The 2-oxoglutarate carrier (OGC) belongs to the mitochondrial carrier protein family whose members are responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. Initially, OGC was characterized by determining substrate specificity, kinetic parameters of transport, inhibitors and molecular probes that form covalent bonds with specific residues. It was shown that OGC specifically transports oxoglutarate and certain carboxylic acids. The substrate specificity combination of OGC is unique, although many of its substrates are also transported by other mitochondrial carriers. The abundant recombinant expression of bovine OGC in Escherichia coli and its ability to functionally reconstitute into proteoliposomes made it possible to deduce the individual contribution of each and every residue of OGC to the transport activity by a complete set of cys-scanning mutants. These studies give experimental support for a substrate binding site constituted by three major contact points on the even-numbered α-helices and identifies other residues as important for transport function through their crucial positions in the structure for conserved interactions and the conformational changes of the carrier during the transport cycle. The results of these investigations have led to utilize OGC as a model protein for understanding the transport mechanism of mitochondrial carriers.

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  1. Department of Biosciences, Biotechnology and Pharmacological Sciences, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via E. Orabona 4, 70125, Bari, Italy

    Magnus Monné, Daniela Valeria Miniero & Giuseppe Fiermonte

  2. Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100, Potenza, Italy

    Magnus Monné & Faustino Bisaccia

  3. Center of Excellence in Comparative Genomics, University of Bari, Via E. Orabona 4, 70125, Bari, Italy

    Giuseppe Fiermonte

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  1. Magnus Monné
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Monné, M., Miniero, D.V., Bisaccia, F. et al. The mitochondrial oxoglutarate carrier: from identification to mechanism. J Bioenerg Biomembr 45, 1–13 (2013). https://doi.org/10.1007/s10863-012-9475-7

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