title: Reversible assembly of the ATP-binding cassette transporter Mdl1 with the F1F0-ATP synthase in mitochondria.
abstract: The half-ABC transporter Mdl1 is localized in the inner membrane of mitochondria and mediates the export of peptides generated upon proteolysis of mitochondrial proteins. The physiological role of the peptides released from mitochondria is currently not understood. Here, we have analyzed the oligomeric state of Mdl1 in the inner membrane and demonstrate nucleotide-dependent binding to the F(1)F(0)-ATP synthase. Mdl1 forms homo-oligomeric, presumably dimeric complexes in the presence of ATP, but was found in association with the F(1)F(0)-ATP synthase at low ATP levels. Mdl1 binds membrane-embedded parts of the ATP synthase complex after the assembly of the F(1) and F(0) moieties. Although independent of Mdl1 activity, complex formation is impaired upon inhibition of the F(1)F(0)-ATP synthase with oligomycin or N,N'-dicyclohexylcarbodiimide. These results are consistent with an activation of Mdl1 upon dissociation from the ATP synthase and suggest a link of peptide export from mitochondria to the activity of the F(1)F(0)-ATP synthase and the cellular energy metabolism.
authors.affiliation: Institut für Genetik, Universität zu Köln, 50674 Köln, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Galluhn
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000737:chemistry; D001692:Biological Transport; D002499:Centrifugation, Density Gradient; D002845:Chromatography; D003001:Cloning, Molecular; D003902:Detergents / Q000494:pharmacology; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000737:chemistry; D005990:Glycerol / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014461:Ultracentrifugation
chemical_list: D018528:ATP-Binding Cassette Transporters; D003902:Detergents; C490069:MDL1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D017830:Octoxynol; D010450:Endopeptidases; C474451:F1F0-ATP synthase; D025261:Mitochondrial Proton-Translocating ATPases; D005990:Glycerol