title: Insertion of bitopic membrane proteins into the inner membrane of mitochondria involves an export step from the matrix.
abstract: The mitochondrial inner membrane contains a large number of polytopic proteins that are derived from prokaryotic ancestors of mitochondria. Little is known about the intramitochondrial sorting of these proteins. We chose two proteins of known topology as examples to study the pathway of insertion into the inner membrane; Mrs2 and Yta10 are bitopic proteins that expose negatively charged loops of different complexity into the intermembrane space. Here we show that both Mrs2 and Yta10 transiently accumulate as sorting intermediates in the matrix before they integrate into the inner membrane. The sorting pathway of both proteins can be separated into two sequential reactions: (i) import into the matrix and (ii) insertion from the matrix into the inner membrane. The latter process was found to depend on the membrane potential and, in this respect, is similar to the insertion of membrane proteins in bacteria. A comparison of the charge distribution of intermembrane space loops in a variety of mitochondrial inner membrane proteins suggests that this mode of "conservative sorting" might be the typical insertion route for polytopic inner membrane proteins that originated from bacterial ancestors.
authors.affiliation: Institut für Physiologische Chemie, Butenandtstrasse 5, 81377 München, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Baumann
authors.forename: Walter
authors.initials: W
authors.lastname: Neupert
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
mesh_terms: D000251:Adenosine Triphosphatases; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D019286:Endopeptidase K / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D007473:Ion Channels; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D024101:Mitochondrial Proteins; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors
chemical_list: D005656:Fungal Proteins; D007473:Ion Channels; C114838:MRS2 protein, S cerevisiae; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D019286:Endopeptidase K; D000251:Adenosine Triphosphatases; C090045:AFG3 protein, S cerevisiae