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OXA1  -  Oxa1p

Saccharomyces cerevisiae S288c

Synonyms: Cytochrome oxidase biogenesis protein OXA1, Mitochondrial inner membrane protein OXA1, Oxidase assembly protein 1, PET1402, YER154W
 
 
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Disease relevance of OXA1

 

High impact information on OXA1

  • Our results indicate that Mdm38 functions as a component of an Oxa1-independent insertion machinery in the inner membrane and that Mdm38 plays a critical role in the biogenesis of the respiratory chain by coupling ribosome function to protein transport across the inner membrane [2].
  • Both Mdm38 and Ylh47 form stable complexes with mitochondrial ribosomes, similar to what has been reported for Oxa1, a central component of the mitochondrial export machinery [2].
  • Oxa1 can be cross-linked to Mrp20, a component of the large ribosomal subunit [3].
  • Ribosome binding to the Oxa1 complex facilitates co-translational protein insertion in mitochondria [4].
  • We propose that the interaction of Oxa1 with the ribosome serves to enhance a coupling of translation and membrane insertion events [3].
 

Biological context of OXA1

  • The nuclear gene OXA1 encodes a protein located within the mitochondrial inner membrane that is required for the biogenesis of both cytochrome c oxidase (Cox) and ATPase [5].
  • Interestingly, the OXA1 gene, located on the yeast chromosome VIII, is adjacent to the gene PET 122, which controls the initiation of cox3 mRNA translation [6].
  • These results suggest that the OXA1 gene is primary required at a post-translational step in cytochrome oxidase biogenesis, probably at the level of assembly, although the oxa1-79 mutation leads to some pleiotropic secondary defects in earlier steps of mitochondrial gene expression [6].
  • Loss of previously described nuclear-mitochondrial signaling genes like RTG1 reduce the level of PDR5 expression and drug resistance seen in rho(o) cells but has no effect on oxa1-induced phenotypes [7].
  • ALB3 is a novel plant gene whose product shows homology to a bacterial membrane protein previously identified in five bacterial species and to a yeast protein, OXA1, and its human homolog [8].
 

Anatomical context of OXA1

  • Oxa1p is a key component of the machinery for the insertion of membrane proteins in mitochondria, and in the yeast Saccharomyces cerevisiae, the deletion of OXA1 impairs the biogenesis of the three respiratory complexes of dual genetic origin [9].
  • ALB3 does not have a function identical to OXA1 because mitochondrial cytochrome oxidase activity is not affected in the mutant, and immunogold labeling as well as chloroplast import experiments performed in vitro demonstrated that the ALB3 protein is present in chloroplast membranes [8].
  • A yeast mitochondrial membrane methyltransferase-like protein can compensate for oxa1 mutations [10].
  • The Oxa1p family plays a key role in this process in organelles and bacteria [11].
  • YidC is homologous to Alb3 and Oxa1 that function in the integration of proteins into the thylakoid membrane of chloroplasts and inner membrane of mitochondria, respectively [12].
 

Associations of OXA1 with chemical compounds

  • Growth on glycerol and cytochrome oxidase assembly are restored to the mutant if it is transformed with the gene encoding authentic subunit IV precursor, a protein carrying a 25-residue transient pre-sequence [13].
  • Substitutions at the Cys ligand positions result in non-functional Cox4 proteins that fail to lead to cytochrome oxidase assembly [14].
  • Flavin adenine dinucleotide binding is the crucial step in alcohol oxidase assembly in the yeast Hansenula polymorpha [15].
 

Physical interactions of OXA1

  • Loss of the mitochondrial genome (rho(0) cell) or elimination of the mitochondrial inner membrane protein Oxa1p causes a dramatic increase in expression of the ATP binding cassette transporter-encoding gene PDR5 in the yeast Saccharomyces cerevisiae [16].
 

Regulatory relationships of OXA1

  • Rmd9p Controls the Processing/Stability of Mitochondrial mRNAs and Its Overexpression Compensates for a Partial Deficiency of Oxa1p in Saccharomyces cerevisiae [17].
 

Other interactions of OXA1

  • Importantly, the signaling pathway used to enhance Pdr3p function in rho(o) cells is not the same as in oxa1 cells [7].
  • Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae [5].
  • Expression of the divergent transcription unit containing the yeast PET122 and OXA1 genes [18].
  • In the absence of Oxa1p, the translocation of the mitochondrially encoded subunit Cox2p to the intermembrane space (also referred to as export) is prevented, and it has been proposed that Oxa1p could be a component of a general mitochondrial export machinery [5].
  • These results indicate Cox18p to be a new member of a group of mitochondrial proteins that function at a late stage of the cytochrome oxidase assembly pathway [19].
  • Oxa1 was found to physically interact with newly synthesized mitochondrially encoded Atp9 protein in a posttranslational manner and in a manner that is not dependent on the C-terminal, matrix-localized region of Oxa1 [20].

References

  1. Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli. Sääf, A., Monné, M., de Gier, J.W., von Heijne, G. J. Biol. Chem. (1998) [Pubmed]
  2. Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery. Frazier, A.E., Taylor, R.D., Mick, D.U., Warscheid, B., Stoepel, N., Meyer, H.E., Ryan, M.T., Guiard, B., Rehling, P. J. Cell Biol. (2006) [Pubmed]
  3. Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1. Jia, L., Dienhart, M., Schramp, M., McCauley, M., Hell, K., Stuart, R.A. EMBO J. (2003) [Pubmed]
  4. Ribosome binding to the Oxa1 complex facilitates co-translational protein insertion in mitochondria. Szyrach, G., Ott, M., Bonnefoy, N., Neupert, W., Herrmann, J.M. EMBO J. (2003) [Pubmed]
  5. Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae. Lemaire, C., Hamel, P., Velours, J., Dujardin, G. J. Biol. Chem. (2000) [Pubmed]
  6. OXA1, a Saccharomyces cerevisiae nuclear gene whose sequence is conserved from prokaryotes to eukaryotes controls cytochrome oxidase biogenesis. Bonnefoy, N., Chalvet, F., Hamel, P., Slonimski, P.P., Dujardin, G. J. Mol. Biol. (1994) [Pubmed]
  7. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. Hallstrom, T.C., Moye-Rowley, W.S. J. Biol. Chem. (2000) [Pubmed]
  8. ALBINO3, an Arabidopsis nuclear gene essential for chloroplast differentiation, encodes a chloroplast protein that shows homology to proteins present in bacterial membranes and yeast mitochondria. Sundberg, E., Slagter, J.G., Fridborg, I., Cleary, S.P., Robinson, C., Coupland, G. Plant Cell (1997) [Pubmed]
  9. The transcriptional activator HAP4 is a high copy suppressor of an oxa1 yeast mutation. Hlavacek, O., Bourens, M., Salone, V., Lachacinski, N., Lemaire, C., Dujardin, G. Gene (2005) [Pubmed]
  10. A yeast mitochondrial membrane methyltransferase-like protein can compensate for oxa1 mutations. Lemaire, C., Guibet-Grandmougin, F., Angles, D., Dujardin, G., Bonnefoy, N. J. Biol. Chem. (2004) [Pubmed]
  11. Role of positively charged transmembrane segments in the insertion and assembly of mitochondrial inner-membrane proteins. Saint-Georges, Y., Hamel, P., Lemaire, C., Dujardin, G. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. The Sec-independent function of Escherichia coli YidC is evolutionary-conserved and essential. van Bloois, E., Nagamori, S., Koningstein, G., Ullers, R.S., Preuss, M., Oudega, B., Harms, N., Kaback, H.R., Herrmann, J.M., Luirink, J. J. Biol. Chem. (2005) [Pubmed]
  13. The first twelve amino acids of a yeast mitochondrial outer membrane protein can direct a nuclear-coded cytochrome oxidase subunit to the mitochondrial inner membrane. Hurt, E.C., Müller, U., Schatz, G. EMBO J. (1985) [Pubmed]
  14. The characterization and role of zinc binding in yeast cox4. Coyne, H.J., Ciofi-Baffoni, S., Banci, L., Bertini, I., Zhang, L., George, G.N., Winge, D.R. J. Biol. Chem. (2007) [Pubmed]
  15. Flavin adenine dinucleotide binding is the crucial step in alcohol oxidase assembly in the yeast Hansenula polymorpha. Evers, M.E., Titorenko, V., Harder, W., ven der Klei, I., Veenhuis, M. Yeast (1996) [Pubmed]
  16. Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the F(0) component of the mitochondrial ATPase. Zhang, X., Moye-Rowley, W.S. J. Biol. Chem. (2001) [Pubmed]
  17. Rmd9p Controls the Processing/Stability of Mitochondrial mRNAs and Its Overexpression Compensates for a Partial Deficiency of Oxa1p in Saccharomyces cerevisiae. Nouet, C., Bourens, M., Hlavacek, O., Marsy, S., Lemaire, C., Dujardin, G. Genetics (2007) [Pubmed]
  18. Expression of the divergent transcription unit containing the yeast PET122 and OXA1 genes. Marathe, S.V., McEwen, J.E. Biochem. Mol. Biol. Int. (1999) [Pubmed]
  19. Cloning and characterization of COX18, a Saccharomyces cerevisiae PET gene required for the assembly of cytochrome oxidase. Souza, R.L., Green-Willms, N.S., Fox, T.D., Tzagoloff, A., Nobrega, F.G. J. Biol. Chem. (2000) [Pubmed]
  20. Oxa1 directly interacts with Atp9 and mediates its assembly into the mitochondrial F1Fo-ATP synthase complex. Jia, L., Dienhart, M.K., Stuart, R.A. Mol. Biol. Cell (2007) [Pubmed]
 
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