title: Partial suppression of Oxa1 mutants by mitochondria-targeted signal recognition particle provides insights into the evolution of the cotranslational insertion systems.
abstract: The biogenesis of hydrophobic membrane proteins involves their cotranslational membrane integration in order to prevent their unproductive aggregation. In the cytosol of bacteria and eukaryotes, membrane targeting of ribosomes that synthesize membrane proteins is achieved by signal recognition particles (SRPs) and their cognate membrane-bound receptors. As is evident from the genomes of fully sequenced eukaryotes, mitochondria generally lack an SRP system. Instead, mitochondrial ribosomes are physically associated with the protein insertion machinery in the inner membrane. Accordingly, deletion of ribosome-binding sites on the Oxa1 insertase and the Mba1 ribosome receptor in yeast leads to severe defects in cotranslational protein insertion and results in respiration-deficient mutants. In this study, we expressed mitochondria-targeted versions of the bacterial SRP protein Ffh and its receptor FtsY in these yeast mutants. Interestingly, Ffh was found to bind to the large subunit of mitochondrial ribosomes, and could relieve, to some degree, the defect of these insertion mutants. Although FtsY could also bind to mitochondrial membranes, it did not improve membrane protein biogenesis in this strain, presumably because of its inability to interact with Ffh. Hence, mitochondrial ribosomes are still able to interact physically and functionally with the bacterial SRP system. Our observations are consistent with a model according to which the protein insertion system in mitochondria evolved in three steps. The loss of genes for hydrophilic polypeptides (step 1) allowed the development of ribosome-binding sites on membrane proteins (step 2), which finally made the existence of an SRP-mediated system dispensable (step 3).
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Ciudad Universitaria, Universidad Nacional Autónoma de México, Distrito Federal, Mexico. sfunes@ifc.unam.mx
authors.forename: Soledad
authors.initials: S
authors.lastname: Funes
authors.forename: Heike
authors.initials: H
authors.lastname: Westerburg
authors.forename: Fabiola
authors.initials: F
authors.lastname: Jaimes-Miranda
authors.forename: Michael W
authors.initials: MW
authors.lastname: Woellhaf
authors.forename: Jose L
authors.initials: JL
authors.lastname: Aguilar-Lopez
authors.forename: Linda
authors.initials: L
authors.lastname: Janßen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonnefoy
authors.forename: Frank
authors.initials: F
authors.lastname: Kauff
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D018271:Signal Recognition Particle / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C082931:Ffh protein, E coli; C087406:FtsY protein, Bacteria; C100490:MBA1 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle; D003576:Electron Transport Complex IV