The mitochondrial oxoglutarate carrier: from identification to mechanism

J Bioenerg Biomembr. 2013 Feb;45(1-2):1-13. doi: 10.1007/s10863-012-9475-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Biological Transport, Active / physiology
  • Cattle
  • Cytoplasm* / chemistry
  • Cytoplasm* / genetics
  • Cytoplasm* / metabolism
  • Escherichia coli
  • Humans
  • Ketoglutaric Acids* / chemistry
  • Ketoglutaric Acids* / metabolism
  • Membrane Transport Proteins* / chemistry
  • Membrane Transport Proteins* / genetics
  • Membrane Transport Proteins* / metabolism
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Mitochondrial Proteins* / chemistry
  • Mitochondrial Proteins* / genetics
  • Mitochondrial Proteins* / metabolism
  • Models, Biological*
  • Mutagenesis
  • Mutation, Missense
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Substrate Specificity

Substances

  • Ketoglutaric Acids
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Recombinant Proteins
  • oxoglutarate translocator