Mitochondrial carriers function as monomers.

TitleMitochondrial carriers function as monomers.
Publication TypeJournal Article
Year of Publication2010
AuthorsKunji, ERS, Crichton, PG
JournalBiochim Biophys Acta
Date Published2010 Jun-Jul
KeywordsAnimals, Carrier Proteins, Chromatography, Affinity, Chromatography, Gel, Cryoelectron Microscopy, Crystallography, X-Ray, Detergents, Electrophoresis, Gel, Two-Dimensional, Freeze Fracturing, Humans, Microscopy, Atomic Force, Mitochondria, Mitochondrial ADP, ATP Translocases, Mitochondrial Proteins, Models, Molecular, Mutagenesis, Site-Directed, Neutron Diffraction, Protein Conformation, Protein Structure, Quaternary, Saccharomyces cerevisiae Proteins, Scattering, Small Angle, Ultracentrifugation

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.

Alternate JournalBiochim. Biophys. Acta
Citation Key10.1016/j.bbabio.2010.03.023
PubMed ID20362544
Grant ListMC_U105663139 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom