Mitochondrial carriers function as monomers

Edmund R. S. Kunji, Paul G. Crichton

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Mitochondrial carriers link biochemical pathways in the mitochondrial matrix and cytosol by transporting metabolites, inorganic ions, nucleotides and cofactors across the mitochondrial inner membrane. Uncoupling proteins that dissipate the proton electrochemical gradient also belong to this protein family. For almost 35. years the general consensus has been that mitochondrial carriers are dimeric in structure and function. This view was based on data from inhibitor binding studies, small-angle neutron scattering, electron microscopy, differential tagging/affinity chromatography, size-exclusion chromatography, analytical ultracentrifugation, native gel electrophoresis, cross-linking experiments, tandem-fusions, negative dominance studies and mutagenesis. However, the structural folds of the ADP/ATP carriers were found to be monomeric, lacking obvious dimerisation interfaces. Subsequently, the yeast ADP/ATP carrier was demonstrated to function as a monomer. Here, we revisit the data that have been published in support of a dimeric state of mitochondrial carriers. Our analysis shows that when critical factors are taken into account, the monomer is the only plausible functional form of mitochondrial carriers. We propose a transport model based on the monomer, in which access to a single substrate binding site is controlled by two flanking salt bridge networks, explaining uniport and strict exchange of substrates.

Original languageEnglish
Pages (from-to)817-831
Number of pages15
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number6-7
Early online date31 Mar 2010
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Detergent
  • Lipid
  • Membrane protein
  • Oligomeric state
  • Protein-protein interaction
  • Transport mechanism

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