COX2

Summary

Gene Symbol: COX2
Description: cytochrome c oxidase subunit 2
Alias: OXI1, OXII, cytochrome c oxidase subunit 2
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Horan S, Bourges I, Taanman J, Meunier B. Analysis of COX2 mutants reveals cytochrome oxidase subassemblies in yeast. Biochem J. 2005;390:703-8 pubmed
    ..The identification of these novel cytochrome oxidase subcomplexes should encourage the reexamination of other yeast mutants. ..
  2. van der Laan M, Wiedemann N, Mick D, Guiard B, Rehling P, Pfanner N. A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria. Curr Biol. 2006;16:2271-6 pubmed
    ..These findings suggest a new coupling mechanism in an energy-transducing membrane. ..
  3. Mick D, Wagner K, van der Laan M, Frazier A, Perschil I, Pawlas M, et al. Shy1 couples Cox1 translational regulation to cytochrome c oxidase assembly. EMBO J. 2007;26:4347-58 pubmed
    ..We suggest that Shy1 links Cox1 translational regulation to complex IV assembly and supercomplex formation. ..
  4. Dienhart M, Stuart R. The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery. Mol Biol Cell. 2008;19:3934-43 pubmed publisher
    ..The physiological implications of the association of AAC with the cytochrome bc(1)-COX-TIM23 supercomplex are also discussed. ..
  5. Perez Martinez X, Butler C, Shingu Vazquez M, Fox T. Dual functions of Mss51 couple synthesis of Cox1 to assembly of cytochrome c oxidase in Saccharomyces cerevisiae mitochondria. Mol Biol Cell. 2009;20:4371-80 pubmed publisher
    ..Regulation of COX1 mRNA translation by Mss51 seems to be an example of a homeostatic mechanism in which a positive effector of gene expression interacts with the product it regulates in a posttranslational assembly process. ..
  6. Gruschke S, Römpler K, Hildenbeutel M, Kehrein K, Kühl I, Bonnefoy N, et al. The Cbp3-Cbp6 complex coordinates cytochrome b synthesis with bc(1) complex assembly in yeast mitochondria. J Cell Biol. 2012;199:137-50 pubmed publisher
    ..This feedback loop regulates protein synthesis at the inner mitochondrial membrane by directly monitoring the efficiency of bc(1) complex assembly. ..
  7. Williams E, Perez Martinez X, Fox T. MrpL36p, a highly diverged L31 ribosomal protein homolog with additional functional domains in Saccharomyces cerevisiae mitochondria. Genetics. 2004;167:65-75 pubmed
    ..of MRPL36 also has been shown to suppress certain types of translation defects encoded within the mitochondrial COX2 mRNA...
  8. Macino G, Coruzzi G, Nobrega F, Li M, Tzagoloff A. Use of the UGA terminator as a tryptophan codon in yeast mitochondria. Proc Natl Acad Sci U S A. 1979;76:3784-5 pubmed
    ..This conclusion is based on the sequence analysis of mitochondrial DNA regions coding for structural genes of cytochrome b, cytochrome oxidase, and the ATPase. ..
  9. Römpler K, Müller T, Juris L, Wissel M, Vukotic M, Hofmann K, et al. Overlapping Role of Respiratory Supercomplex Factor Rcf2 and Its N-terminal Homolog Rcf3 in Saccharomyces cerevisiae. J Biol Chem. 2016;291:23769-23778 pubmed
    ..Furthermore, our data suggest an association of all three Rcf proteins with the bc1 complex in the absence of a functional cytochrome c oxidase and identify a supercomplex independent interaction network of the Rcf proteins. ..

More Information

Publications57

  1. Pel H, Maat C, Rep M, Grivell L. The yeast nuclear gene MRF1 encodes a mitochondrial peptide chain release factor and cures several mitochondrial RNA splicing defects. Nucleic Acids Res. 1992;20:6339-46 pubmed
    ..disturbed in the expression of the mitochondrial genes encoding cytochrome c oxidase subunit 1 and 2, COX1 and COX2. For COX1 this defect has been attributed to an impaired processing of several introns...
  2. Mick D, Vukotic M, Piechura H, Meyer H, Warscheid B, Deckers M, et al. Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria. J Cell Biol. 2010;191:141-54 pubmed publisher
    ..Our data indicate that Coa1 binding to sequestered Mss51 in complex with Cox14, Coa3, and Cox1 is essential for full inactivation. ..
  3. Esser K, Pratje E, Michaelis G. SOM 1, a small new gene required for mitochondrial inner membrane peptidase function in Saccharomyces cerevisiae. Mol Gen Genet. 1996;252:437-45 pubmed
    ..mitochondrial inner membrane peptidase responsible for the proteolytic processing of cytochrome oxidase subunit 2 (Cox2) and cytochrome b2 (Cytb2)...
  4. Chen Y, Taylor E, Dephoure N, Heo J, Tonhato A, Papandreou I, et al. Identification of a protein mediating respiratory supercomplex stability. Cell Metab. 2012;15:348-60 pubmed publisher
    ..We suggest that Rcf1 is a member of an evolutionarily conserved protein family that acts to promote respiratory supercomplex assembly and activity. ..
  5. Hell K, Herrmann J, Pratje E, Neupert W, Stuart R. Oxa1p, an essential component of the N-tail protein export machinery in mitochondria. Proc Natl Acad Sci U S A. 1998;95:2250-5 pubmed
    ..Thus, Oxa1p represents a component of a general export machinery of the mitochondrial inner membrane. ..
  6. Pacheu Grau D, Bareth B, Dudek J, Juris L, Vögtle F, Wissel M, et al. Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies. Cell Metab. 2015;21:823-33 pubmed publisher
    ..COX1 and COX2 contain heme and copper redox centers, which are integrated during assembly of the enzyme...
  7. Geier B, Schagger H, Ortwein C, Link T, Hagen W, Brandt U, et al. Kinetic properties and ligand binding of the eleven-subunit cytochrome-c oxidase from Saccharomyces cerevisiae isolated with a novel large-scale purification method. Eur J Biochem. 1995;227:296-302 pubmed
    ..This high content of fast enzyme was also reflected in the characteristics of optical and EPR spectra for cytochrome-c oxidase purified with our method. ..
  8. Ghosh A, Pratt A, Soma S, Theriault S, Griffin A, Trivedi P, et al. Mitochondrial disease genes COA6, COX6B and SCO2 have overlapping roles in COX2 biogenesis. Hum Mol Genet. 2016;25:660-71 pubmed publisher
    ..factor, COA6, and our previous work linked Coa6 function to mitochondrial copper metabolism and expression of Cox2, a copper-containing subunit of CcO. However, the precise role of Coa6 in Cox2 biogenesis remained unknown...
  9. Fox T. Five TGA "stop" codons occur within the translated sequence of the yeast mitochondrial gene for cytochrome c oxidase subunit II. Proc Natl Acad Sci U S A. 1979;76:6534-8 pubmed
    ..It is concluded that TGA is translated in yeast mitochondria, most probably as tryptophan. ..
  10. Fiumera H, Dunham M, Saracco S, Butler C, Kelly J, Fox T. Translocation and assembly of mitochondrially coded Saccharomyces cerevisiae cytochrome c oxidase subunit Cox2 by Oxa1 and Yme1 in the absence of Cox18. Genetics. 2009;182:519-28 pubmed publisher
    ..In Saccharomyces cerevisiae, Oxa1 and its paralog, Cox18, are required for assembly of Cox2, a mitochondrially encoded subunit of cytochrome c oxidase...
  11. Shingu Vazquez M, Camacho Villasana Y, Sandoval Romero L, Butler C, Fox T, Perez Martinez X. The carboxyl-terminal end of Cox1 is required for feedback assembly regulation of Cox1 synthesis in Saccharomyces cerevisiae mitochondria. J Biol Chem. 2010;285:34382-9 pubmed publisher
    ..Our data suggest a novel activity of Pet54 required for normal synthesis of Cox1 that is independent of the Cox1 C-terminal end. ..
  12. Cameron V, Fox T, Poyton R. Isolation and characterization of a yeast strain carrying a mutation in the mitochondrial promoter for COX2. J Biol Chem. 1989;264:13391-4 pubmed
    ..yeast strain has been isolated and shown genetically to carry a mutation in the subunit II structural gene COX2. The respiration-deficient strain produces no subunit II polypeptide and is missing two major transcripts of the ..
  13. Tatsuta T, Model K, Langer T. Formation of membrane-bound ring complexes by prohibitins in mitochondria. Mol Biol Cell. 2005;16:248-59 pubmed
    ..Implications of these findings for proposed cellular activities of prohibitins are discussed. ..
  14. Elliott L, Saracco S, Fox T. Multiple roles of the Cox20 chaperone in assembly of Saccharomyces cerevisiae cytochrome c oxidase. Genetics. 2012;190:559-67 pubmed publisher
    The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the ..
  15. Lode A, Paret C, Rödel G. Molecular characterization of Saccharomyces cerevisiae Sco2p reveals a high degree of redundancy with Sco1p. Yeast. 2002;19:909-22 pubmed
    ..Our data suggest that Sco2p is involved in the transfer of copper to Cox2p, but that this activity is insufficient for oxidative growth and not able to substitute for Sco1p activity. ..
  16. McStay G, Su C, Thomas S, Xu J, Tzagoloff A. Characterization of assembly intermediates containing subunit 1 of yeast cytochrome oxidase. J Biol Chem. 2013;288:26546-56 pubmed publisher
  17. Deckers M, Balleininger M, Vukotic M, Römpler K, Bareth B, Juris L, et al. Aim24 stabilizes respiratory chain supercomplexes and is required for efficient respiration. FEBS Lett. 2014;588:2985-92 pubmed publisher
    ..Deletion of AIM24 strongly affects activity of the respiratory chain and induces a growth defect on non-fermentable medium. Our data indicate that Aim24 has a function in stabilizing the respiratory chain supercomplexes. ..
  18. McStay G, Su C, Tzagoloff A. Stabilization of Cox1p intermediates by the Cox14p-Coa3p complex. FEBS Lett. 2013;587:943-9 pubmed publisher
  19. Foury F, Roganti T, Lecrenier N, Purnelle B. The complete sequence of the mitochondrial genome of Saccharomyces cerevisiae. FEBS Lett. 1998;440:325-31 pubmed
    ..Our data suggest that shuffling of mobile elements plays an important role in the remodelling of the yeast mitochondrial genome. ..
  20. Fontanesi F, SOTO I, Horn D, Barrientos A. Mss51 and Ssc1 facilitate translational regulation of cytochrome c oxidase biogenesis. Mol Cell Biol. 2010;30:245-59 pubmed publisher
    ..We conclude that Ssc1, by interacting with Mss51 and Mss51-containing complexes, plays a critical role in Cox1 biogenesis, COX assembly, and the translational regulation of these processes. ..
  21. Supekova L, Supek F, Greer J, Schultz P. A single mutation in the first transmembrane domain of yeast COX2 enables its allotopic expression. Proc Natl Acad Sci U S A. 2010;107:5047-52 pubmed publisher
    ..control the mitochondrial gene transfer/retention process, we have investigated the barriers to transfer of yeast COX2, a mitochondrial gene coding for a subunit of cytochrome c oxidase complex...
  22. Mulero J, Fox T. Alteration of the Saccharomyces cerevisiae COX2 mRNA 5'-untranslated leader by mitochondrial gene replacement and functional interaction with the translational activator protein PET111. Mol Biol Cell. 1993;4:1327-35 pubmed
    ..by which the nuclearly encoded PET111 protein specifically activates translation of the mitochondrially coded COX2 mRNA...
  23. Fox T. Genetic and physical analysis of the mitochondrial gene for subunit II of yeast cytochrome c oxidase. J Mol Biol. 1979;130:63-82 pubmed
  24. Shen H, Walters D, Mueller D. Introduction of the chloroplast redox regulatory region in the yeast ATP synthase impairs cytochrome c oxidase. J Biol Chem. 2008;283:32937-43 pubmed publisher
    ..These results indicate that the chimeric ATP synthase containing cysteine, but not serine, decreases the expression or assembly of cytochrome c oxidase with little effect on the activity of the ATP synthase. ..
  25. Conte A, Papa B, Ferramosca A, Zara V. The dimerization of the yeast cytochrome bc1 complex is an early event and is independent of Rip1. Biochim Biophys Acta. 2015;1853:987-95 pubmed publisher
    ..Finally, a new model of cytochrome bc1 complex assembly, in which distinct intermediates sequentially interact during bc1 maturation, has been proposed. ..
  26. Strecker V, Kadeer Z, Heidler J, Cruciat C, Angerer H, Giese H, et al. Supercomplex-associated Cox26 protein binds to cytochrome c oxidase. Biochim Biophys Acta. 2016;1863:1643-52 pubmed publisher
    ..A population of Cox26 was observed to exist in a disulfide bond partnership with the Cox2 subunit of complex IV...
  27. Cruz Torres V, Vázquez Acevedo M, García Villegas R, Perez Martinez X, Mendoza Hernandez G, Gonzalez Halphen D. The cytosol-synthesized subunit II (Cox2) precursor with the point mutation W56R is correctly processed in yeast mitochondria to rescue cytochrome oxidase. Biochim Biophys Acta. 2012;1817:2128-39 pubmed publisher
    Deletion of the yeast mitochondrial gene COX2 encoding subunit 2 (Cox2) of cytochrome c oxidase (CcO) results in loss of respiration (?cox2 strain). Supekova et al...
  28. Lode A, Kuschel M, Paret C, Rödel G. Mitochondrial copper metabolism in yeast: interaction between Sco1p and Cox2p. FEBS Lett. 2000;485:19-24 pubmed
    ..These amino acids, which are conserved among the members of the Sco1p family, have been suggested to act in the reduction of the cysteines in the copper binding center of Cox2p and are discussed as ligands for copper. ..
  29. Gebert M, Schrempp S, Mehnert C, Heißwolf A, Oeljeklaus S, Ieva R, et al. Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes. J Cell Biol. 2012;197:595-604 pubmed publisher
    ..We conclude that Mgr2 is a coupling factor of the presequence translocase crucial for cell growth at elevated temperature and for efficient protein import. ..
  30. Strogolova V, Furness A, Robb McGrath M, Garlich J, Stuart R. Rcf1 and Rcf2, members of the hypoxia-induced gene 1 protein family, are critical components of the mitochondrial cytochrome bc1-cytochrome c oxidase supercomplex. Mol Cell Biol. 2012;32:1363-73 pubmed publisher
    ..Based on our findings, we propose a model where the Hig1 proteins regulate the COX enzyme activity through Cox3 and associated Cox12 protein, in a manner that may be influenced by the neighboring AAC proteins. ..
  31. Su C, McStay G, Tzagoloff A. Assembly of the rotor component of yeast mitochondrial ATP synthase is enhanced when Atp9p is supplied by Atp9p-Cox6p complexes. J Biol Chem. 2014;289:31605-16 pubmed publisher
  32. Coruzzi G, Tzagoloff A. Assembly of the mitochondrial membrane system. DNA sequence of subunit 2 of yeast cytochrome oxidase. J Biol Chem. 1979;254:9324-30 pubmed
    ..The DNA segment of DS200/A1 has been located on the wild type mitochondrial DNA by comparative restriction mapping. The orientation of the COOH and NH2 termini and the direction of transcription of the gene have been determined. ..
  33. Horn D, Fontanesi F, Barrientos A. Exploring protein-protein interactions involving newly synthesized mitochondrial DNA-encoded proteins. Methods Mol Biol. 2008;457:125-39 pubmed
  34. Rigby K, Cobine P, Khalimonchuk O, Winge D. Mapping the functional interaction of Sco1 and Cox2 in cytochrome oxidase biogenesis. J Biol Chem. 2008;283:15015-22 pubmed publisher
    Sco1 is implicated in the copper metallation of the Cu(A) site in Cox2 of cytochrome oxidase. The structure of Sco1 in the metallated and apo-conformers revealed structural dynamics primarily in an exposed region designated loop 8...
  35. Hell K, Neupert W, Stuart R. Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA. EMBO J. 2001;20:1281-8 pubmed
    ..Taken together, we conclude that the Oxa1 complex represents a general membrane protein insertion machinery in the inner membrane of mitochondria. ..
  36. Meyer W, Bauer M, Pratje E. A mutation in cytochrome oxidase subunit 2 restores respiration of the mutant pet ts1402. Curr Genet. 1997;31:401-7 pubmed
    ..results in an accumulation of the precursor form of the mitochondrially encoded subunit 2 of cytochrome oxidase (Cox2) and temperature-sensitive respiration...
  37. Fiumera H, Broadley S, Fox T. Translocation of mitochondrially synthesized Cox2 domains from the matrix to the intermembrane space. Mol Cell Biol. 2007;27:4664-73 pubmed
    The N-terminal and C-terminal domains of mitochondrially synthesized cytochrome c oxidase subunit II, Cox2, are translocated through the inner membrane to the intermembrane space (IMS)...
  38. Nittis T, George G, Winge D. Yeast Sco1, a protein essential for cytochrome c oxidase function is a Cu(I)-binding protein. J Biol Chem. 2001;276:42520-6 pubmed
    ..Thus, the function of Sco1 correlates with Cu(I) binding. Data obtained from size-exclusion chromatography experiments with mitochondrial lysates suggest that full-length Sco1 may be oligomeric in vivo. ..
  39. Hell K, Tzagoloff A, Neupert W, Stuart R. Identification of Cox20p, a novel protein involved in the maturation and assembly of cytochrome oxidase subunit 2. J Biol Chem. 2000;275:4571-8 pubmed
    ..We propose that Cox20p acts as a membrane-bound chaperone necessary for cleavage of pCox2p and for interaction of the mature protein with other subunits of cytochrome oxidase in a later step of the assembly process. ..
  40. Green Willms N, Fox T, Costanzo M. Functional interactions between yeast mitochondrial ribosomes and mRNA 5' untranslated leaders. Mol Cell Biol. 1998;18:1826-34 pubmed
    ..in two new nuclear genes that suppress translation defects due to certain alterations in the 5'-UTLs of both the COX2 and COX3 mRNAs, indicating a general function in translational activation...
  41. Mulero J, Fox T. Reduced but accurate translation from a mutant AUA initiation codon in the mitochondrial COX2 mRNA of Saccharomyces cerevisiae. Mol Gen Genet. 1994;242:383-90 pubmed
    We have changed the translation initiation codon of the COX2 mRNA of Saccharomyces cerevisiae from AUG to AUA, generating a mutation termed cox2-10...
  42. Pratje E, Mannhaupt G, Michaelis G, Beyreuther K. A nuclear mutation prevents processing of a mitochondrially encoded membrane protein in Saccharomyces cerevisiae. EMBO J. 1983;2:1049-54 pubmed
    Subunit II of cytochrome oxidase is encoded by the mitochondrial OXI1 gene in Saccharomyces cerevisiae. The temperature-sensitive nuclear pet mutant ts2858 has an apparent higher mol. wt...
  43. Taanman J, Capaldi R. Purification of yeast cytochrome c oxidase with a subunit composition resembling the mammalian enzyme. J Biol Chem. 1992;267:22481-5 pubmed
    ..The enzyme isolated in lauryl maltoside contains these same nine different polypeptides and three others, including homologues of subunits VIa and VIb of the mammalian enzyme. ..
  44. Buttner S, Ruli D, Vögtle F, Galluzzi L, Moitzi B, Eisenberg T, et al. A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis. EMBO J. 2011;30:2779-92 pubmed publisher
    ..Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms. ..
  45. Sikora J, Towpik J, Graczyk D, Kistowski M, Rubel T, Poznanski J, et al. Yeast prion [PSI+] lowers the levels of mitochondrial prohibitins. Biochim Biophys Acta. 2009;1793:1703-9 pubmed publisher
    ..From this set we focused on prohibitins, Phb1 and Phb2, and the mitochondrially synthesized Cox2 subunit of cytochrome oxidase...
  46. Keil M, Bareth B, Woellhaf M, Peleh V, Prestele M, Rehling P, et al. Oxa1-ribosome complexes coordinate the assembly of cytochrome C oxidase in mitochondria. J Biol Chem. 2012;287:34484-93 pubmed publisher
    ..This points to a role for Oxa1 in the spatial coordination of the ribosome with assembly factors that are critical for enzyme biogenesis. ..
  47. Williams E, Bsat N, Bonnefoy N, Butler C, Fox T. Alteration of a novel dispensable mitochondrial ribosomal small-subunit protein, Rsm28p, allows translation of defective COX2 mRNAs. Eukaryot Cell. 2005;4:337-45 pubmed
    Mutations affecting the RNA sequence of the first 10 codons of the Saccharomyces cerevisiae mitochondrial gene COX2 strongly reduce translation of the mRNA, which encodes the precursor of cytochrome c oxidase subunit II...
  48. Garlich J, Strecker V, Wittig I, Stuart R. Mutational Analysis of the QRRQ Motif in the Yeast Hig1 Type 2 Protein Rcf1 Reveals a Regulatory Role for the Cytochrome c Oxidase Complex. J Biol Chem. 2017;292:5216-5226 pubmed publisher
    ..We speculate that the Rcf1/Hig1 proteins play a role in the incorporation and/or remodeling of lipids, in particular cardiolipin, into complex IV and. possibly, other mitochondrial proteins such as ADP/ATP carrier proteins. ..