title: The membrane-bound GTPase Guf1 promotes mitochondrial protein synthesis under suboptimal conditions.
abstract: Recently, the bacterial elongation factor LepA was identified as critical for the accuracy of in vitro translation reactions. Extremely well conserved homologues of LepA are present throughout bacteria and eukaryotes, but the physiological relevance of these proteins is unclear. Here we show that the yeast counterpart of LepA, Guf1, is located in the mitochondrial matrix and tightly associated with the inner membrane. It binds to mitochondrial ribosomes in a GTP-dependent manner. Mutants lacking Guf1 show cold- and heat-sensitive growth defects on non-fermentable carbon sources that are especially pronounced under nutrient-limiting conditions. The cold sensitivity is explained by diminished rates of protein synthesis at low temperatures. At elevated temperatures, Guf1-deficient mutants exhibit defects in the assembly of cytochrome oxidase, suggesting that the polypeptides produced are not functional. Moreover, Guf1 mutants exhibit synthetic growth defects with mutations of the protein insertase Oxa1. These observations show a critical role for Guf1 in vivo. The observed defects in Guf1-deficient mitochondria are consistent with a function of Guf1 as a fidelity factor of mitochondrial protein synthesis.
authors.affiliation: Institute of Physiological Chemistry, University of Munich, 81377 Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bauerschmitt
authors.forename: Soledad
authors.initials: S
authors.lastname: Funes
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
mesh_terms: D002462:Cell Membrane / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010448:Peptide Initiation Factors; D010455:Peptides / Q000737:chemistry; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D013045:Species Specificity; D013696:Temperature; D035602:Transcriptional Elongation Factors / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; C515651:LepA protein, E coli; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C090858:OXA1 protein; D010448:Peptide Initiation Factors; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C530260:Guf1 protein, S cerevisiae