Thomas W. O’Brien, Ph.D. Home Page

Dr. Thomas O'Brien

Dr. Thomas O’Brien on a National Geographic Expedition to Patagonia

Selected Publications | Research PresentationsSurprises from Mitoribosome Research

Research Focus

The discovery of ribosomes in mitochondria in Dr. O’Brien’s laboratory foreshadowed the surprising diversity of ribosome types in nature.

Mammalian mitochondrial ribosomes differ unexpectedly from bacterial and cytoplasmic ribosomes, as well as other kinds of mitochondrial ribosomes.

The bovine mitochondrial ribosome is being developed as a model system for the study of mammalian mitochondrial ribosomes, to address several questions related to the structure, function, biosynthesis and evolution of these interesting ribosomes. Current projects include structural/functional characterization of the novel GTP binding site on mitochondrial ribosomes, initiation factors and mRNA binding to mitochondrial ribosomes, a structural model for mitochondrial ribosomes, and the structure, organization and expression of genes for mitochondrial ribosomal proteins.

 


Selected Publications:

The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.
Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW.
Mol Genet Metab. 2012 Jul;106(3):385-94.

Nuclear MRP genes and mitochondrial disease.
O’Brien TW, O’Brien BJ, Norman RA.
Gene. 2005 Jul 18;354:147-51. Review.

Mitochondrial ribosomal proteins: candidate genes for mitochondrial disease.
Sylvester JE, Fischel-Ghodsian N, Mougey EB, O’Brien TW.
Genet Med. 2004 Mar-Apr;6(2):73-80. Review.

Properties of human mitochondrial ribosomes.
O’Brien TW.
IUBMB Life. 2003 Sep;55(9):505-13. Review.

Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease.
O’Brien TW.
Gene. 2002 Mar 6;286(1):73-9.

Heart-specific splice-variant of a human mitochondrial ribosomal protein (mRNA processing; tissue specific splicing).
Spirina O, Bykhovskaya Y, Kajava AV, O’Brien TW, Nierlich DP, Mougey EB, Sylvester JE, Graack HR, Wittmann-Liebold B, Fischel-Ghodsian N.
Gene. 2000 Dec 31;261(2):229-34.

Mammalian mitochondrial ribosomal proteins (4). Amino acid sequencing, characterization, and identification of corresponding gene sequences.
O’Brien TW, Liu J, Sylvester JE, Mougey EB, Fischel-Ghodsian N, Thiede B, Wittmann-Liebold B, Graack HR.
J Biol Chem. 2000 Jun 16;275(24):18153-9.

Identification of mammalian mitochondrial ribosomal proteins (MRPs) by N-terminal sequencing of purified bovine MRPs and comparison to data bank sequences: the large subribosomal particle.
Graack HR, Bryant ML, O’Brien TW.
Biochemistry. 1999 Dec 14;38(50):16569-77.

Mammalian mitochondrial ribosomal proteins (2). Amino acid sequencing, characterization, and identification of corresponding gene sequences.
O’Brien TW, Fiesler SE, Denslow ND, Thiede B, Wittmann-Liebold B, Mougey EB, Sylvester JE, Graack HR.
J Biol Chem. 1999 Dec 17;274(51):36043-51.

Site-directed hydroxyl radical probing of 30S ribosomal subunits by using Fe(II) tethered to an interruption in the 16S rRNA chain.
Samaha RR, Joseph S, O’Brien B, O’Brien TW, Noller HF.
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):366-70.

Independent in vitro assembly of a ribonucleoprotein particle containing the 3′ domain of 16S rRNA.
Samaha RR, O’Brien B, O’Brien TW, Noller HF.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7884-8.

Phosphorylation of rabbit reticulocyte guanine nucleotide exchange factor in vivo. Identification of putative casein kinase II phosphorylation sites.
Aroor AR, Denslow ND, Singh LP, O’Brien TW, Wahba AJ.
Biochemistry. 1994 Mar 22;33(11):3350-7.

Proteins of mammalian mitochondrial ribosomes.
Pietromonaco SF, Denslow ND, O’Brien TW.
Biochimie. 1991 Jun;73(6):827-35.

Bovine mitochondrial ribosomes possess a high affinity binding site for guanine nucleotides.
Denslow ND, Anders JC, O’Brien TW.
J Biol Chem. 1991 May 25;266(15):9586-90.

The translation system of mammalian mitochondria.
O’Brien TW, Denslow ND, Anders JC, Courtney BC.
Biochim Biophys Acta. 1990 Aug 27;1050(1-3):174-8.

Mechanism of mRNA binding to bovine mitochondrial ribosomes.
Denslow ND, Michaels GS, Montoya J, Attardi G, O’Brien TW.
J Biol Chem. 1989 May 15;264(14):8328-38.

Interaction of bovine mitochondrial ribosomes with Escherichia coli initiation factor 3 (IF3).
Denslow ND, LiCata VJ, Gualerzi C, O’Brien TW.
Biochemistry. 1988 May 3;27(9):3521-7.

RNA binding proteins of the large subunit of bovine mitochondrial ribosomes.
Piatyszek MA, Denslow ND, O’Brien TW.
Nucleic Acids Res. 1988 Mar 25;16(6):2565-83.

Production of monospecific antibodies to a low-abundance hepatic membrane protein using nitrocellulose immobilized protein as antigen.
Chiles TC, O’Brien TW, Kilberg MS.
Anal Biochem. 1987 May 15;163(1):136-42.

Evolution of proteins in mammalian cytoplasmic and mitochondrial ribosomes.
Pietromonaco SF, Hessler RA, O’Brien TW.
J Mol Evol. 1986;24(1-2):110-7.

Site of synthesis of the proteins of mammalian mitochondrial ribosomes. Evidence from cultured bovine cells.
Schieber GL, O’Brien TW.
J Biol Chem. 1985 May 25;260(10):6367-72.

Organization of proteins in mammalian mitochondrial ribosomes. Accessibility to lactoperoxidase-catalyzed radioiodination.
Denslow ND, O’Brien TW.
J Biol Chem. 1984 Aug 10;259(15):9867-73.

Reconstitution of 50 S ribosomal subunits from Bacillus stearothermophilus with 5 S RNA from spinach chloroplasts and low-Mr RNA from mitochondria of Locusta migratoria and bovine liver.
Vogel DW, Hartmann RK, Bartsch M, Subramanian AR, Kleinow W, O’Brien TW, Pieler T, Erdmann VA.
FEBS Lett. 1984 Apr 9;169(1):67-72.

Protein composition of the bovine mitochondrial ribosome.
Matthews DE, Hessler RA, Denslow ND, Edwards JS, O’Brien TW.
J Biol Chem. 1982 Aug 10;257(15):8788-94.

Extraction of proteins from the large subunit of bovine mitochondrial ribosomes under nondenaturing conditions.
Schieber GL, O’Brien TW.
J Biol Chem. 1982 Aug 10;257(15):8781-7.

A physical map of bovine mitochondrial DNA from a single animal.
Laipis PJ, Hauswirth WW, O’Brien TW, Michaels GS.
Biochim Biophys Acta. 1979 Nov 22;565(1):22-32.

 

Denslow, N.D., and O’Brien, T.W.,Elongation Factors EF-G from E. coli and Mammalian Mitochondria are not functionally interchangeable. Biochem. Biophys. Res.Commun., 90:1257-1265 (1979).

Denslow, N.D. and O’Brien, T.W., Antibiotic Susceptibility of the Peptidyl Transferase Locus of Bovine Mitochondrial Ribosomes. Eur. J. Biochem., 91:444-448(1978).

Matthews, D.E., Hessler, R.A. and O’Brien,T.W., Rapid Evolutionary Divergence of Proteins in Mammalian Mitochondrial Ribosomes. FEBS Letters, 86:76(1978).

O’Brien, T.W., Transcription and Translation in Mitochondria. In: International Cell Biology,1976-77, B.R. Brinkley and Keith R. Porter (eds.), The Rockefeller University Press, New York (1977) pp. 245-255.

O’Brien, T.W., Matthews, D.E. and Denslow, N.D., Protein Composition of the Bovine Mitochondrial Ribosome. In: The Genetics and Biogenesis of Chloroplasts and Mitochondria, T. Bucher, W. Neupert, W. Sebald and S. Werner (eds.), North-Holland Publishing Co., Amsterdam (1977) pp. 741-748.

O’Brien, T.W., and Matthews, D.E., Mitochondrial Ribosomes. In: Handbook of Genetics, Vol. 5, Robert C. King (ed.), Plenum Publishing Co., 1976, pp. 535-80.

O’Brien, T.W., Mitochondrial Protein Synthesis. In: Protein Synthesis, Vol. 2, E.H. McConkey (ed.), Marcel Dekker, Inc., New York, 1976, pp. 249-307.

Hamilton, M.G. and O’Brien, T.W.,Ultracentrifugal Characterization of the Mitochondrial Ribosome and Subribosomal Particles of Bovine Liver: Molecular Size and Composition. Biochemistry, 13:5400 (1974).

Denslow, N.D. and O’Brien, T.W.,Susceptibility of 55S Mitochondrial Ribosomes to Antibiotics Inhibitory to Prokaryotic Ribosomes: Lincomycin, Chloramphenicol, and PA114A. Biochem. Biophys. Res. Commun., 57:9 (1974).

O’Brien, T.W., The General Occurrence of 55S Ribosomes in Mammalian Liver Mitochondria. J. Biol. Chem.,245:3409 (1971).

O’Brien, T.W. and Kalf, G.F., Ribosomes from Rat Liver Mitochondria. II. Partial Characterization. J. Biol. Chem., 242:2180 (1967).

O’Brien, T.W. and Kalf, G.F., Ribosomes from Rat Liver Mitochondria. I. Isolation Procedure and Contamination Studies. J. Biol. Chem., 242:2172 (1967).

Research Presentations:

Liu, J. and O’Brien, T.W. Structural Disposition of Mammalian Mitoribosomal Proteins: Bovine MRP-L31, a Member of the Eubacterial L7/L12 Superfamily. International Conference on the Ribosome: Structure, Function, Antibiotics and Cellular Interactions, Helsingoer, Denmark, June 13 – 17, 1999.

Graack, H.-R., O’Brien, T. W., and Wittmann-Liebold, B. Mitochondrial Ribosomal Proteins (MRPs) from Yeast and Mammals: Identification, Characterization, and Evolution. 23rd Annual meeting of the German Cell Biology Society. Rostock, March 14-18, 1999; Eur. J. Cell Biol. (1999) 78 suppl. 49, 91

Liu, J., Barnoski B. L., and O’Brien T. W. Structure and organization of human genes for mitoribosomal proteins: the homologue of the prokaryotic ribosomal protein L7/L12. Annual Meeting of the American Society for Human Genetics, Denver, October 27 – 31, 1998.

O’Brien, T. W., Faunce, W. and Cogle,C. RNA Domains in Mammalian Mitochondrial Ribosomes, Third Annual Meeting of the RNA Society, Madison, May 26-31, 1998.

Liu, J. and O’Brien, T. W. Characterizationof Genomic DNA for Bovine Mitoribosomal Protein L31, a Member of the Eubacterial L7/L12 Superfamily, Annual Meeting of the American Society for Biochemistry and Molecular Biology, Washington, D.C., May 16-20, 1998.

Liu, J. and O’Brien, T. W. Cloning of cDNAand Genomic DNA for Bovine Mitoribosomal Protein L31, a Member of the Eubacterial L7/L12 Superfamily, 17th International Congress of Biochemistry and Molecular Biology, San Francisco, August 24-29, 1997.

O’Brien, T., Faunce, W., Cogle, C. and Heck, R. RNA Domains in Mammalian Mitochondrial Ribosomes, RNA Structure Symposium, University of California, Santa Cruz, June 25-26, 1997.

O’Brien, T., Faunce, W. and Cogle, C. RNA Disposition in Mammalian Mitochondrial Ribosomes. Second Annual Meeting of the RNA Society, Banff, Alberta, Canada, May 27-June 1, 1997.

Liu, J. and O’Brien, T.W. Cloning of cDNA for Bovine Mitoribosomal Protein L31, A Member of the Eubacterial L7/12 Superfamily. International Congress on Cell Biology, SanFrancisco, California, December 7-11, 1996.

Liu, J., Anders, J. C. and O’Brien, T. W.GTP Binding Protein in the Small Subunit of Bovine Mitochondrial Ribosomes: a Protein in Search of Function. Cold Spring Harbor Meeting on Translational Control, September 4 – 8, 1996.

Samaha, R., Joseph, S., O’Brien, B.,O’Brien, T. W. and Noller, H.F. Site-Directed Hydroxyl Radical Probing Using 30S Ribosomal Subunits Assembled in vitro from Synthetic 16S rRNA Fragments. The First Annual Meeting of the RNA Society, Madison, Wisconsin, May 28-June 2, 1996.

Liu, J., Bryant, M. and O’Brien, T.W.Purification, Sequence Analysis and Cloning of cDNA for Bovine Mitoribosomal Proteins L31, Superfamily. The First Annual Meeting ofthe RNA Society, Madison, Wisconsin, May 28-June 2, 1996.

Liu, J. and O’Brien, T.W. Cloning of cDNA for Bovine Mitoribosomal Protein L31, A Member of the Eubacterial L7/12 Superfamily. Gordon Research Conference on Mitochondria and Chloroplasts, June 16-21, 1996.

O’Brien, T. W., Faunce, W. H., O’Brien, B.J., Cogle, C.R. and Hussain, S. RNA Domains in Mitochondrial Ribosomes: Disposition of RNA in the Small Subunit of Bovine Mitochondrial Ribosomes. The First Annual Meeting of the RNA Society, Madison, Wisconsin May 28-June 2, 1996.

Liu, J., Anders, J.C., and O’Brien, T.W. Purification, Sequence Analysis and Cloning of cDNA for the GTP Binding Protein in the Small Subunit of Bovine Mitochondrial Ribosomes, Ninth Symposium of the Protein Society, Boston, July 8-12, 1995.

Liu, J., Anders, J.C., and O’Brien,T.W. Purification, Sequence Analysis and Cloning of cDNA fort he GTP Binding Protein in the Small Subunit of Bovine Mitochondrial Ribosomes, International Conference on the Structure and Function of the Ribosome, “Frontiers in Translation”, Victoria, B.C., May 20-25, 1995.

O’Brien, T.W., Faunce, W.H., O’Brien, B.,Cogle, C.R, and Hussain, S. RNA Domains in Mitochondrial Ribosomes: Disposition of RNA in the Small Subunit of Bovine Mitochondrial Ribosomes, International Conference on the Structure and Function of the Ribosome, “Frontiers in Translation”, Victoria, B.C., May 20-25, 1995.

O’Brien, T.W., Liu, J., and Anders,J.C. Sequence and Properties of the GTP Binding Protein in Mammalian Mitochondrial Ribosomes, International Symposium on Thirty Years of Progress in Mitochondrial Bioenergetics and Molecular Biology, Selva di Fasano, Italy, October 7-10, 1994.

O’Brien, T.W., Faunce, W.H., O’Brien, B.J.,and Cogle, C.R. RNA Domains in Mitochondrial Ribosomes; Disposition of RNA in the small subunit of Bovine Mitochondrial Ribosomes, International Symposium on Thirty Years of Progress in Mitochondrial Bioenergetics and Molecular Biology, Selva di Fasano, Italy, October 7-10, 1994.

Liu, J., Anders, J.C., and O’Brien, T.W.Amino Acid Sequence Analysis and Cloning of cDNA for the GTP Binding Protein in the Small Subunit of Bovine Mitochondrial Ribosomes, Cold Spring Harbor Meeting on Translational Control, August 24-28,1994.

Liu, J., Anders, J.C., and O’Brien, T.W. Purification, Sequence Analysis and Cloning of cDNA for the GTP Binding Protein in the small subunit of Bovine Mitochondrial Ribosomes, Abstract LBl9, American Society for Biochemistry and Molecular Biology Meeting, Washington, D.C., May 21-25, 1994.

O’Brien, T.W., Faunce, W.H., O’Brien, B.J.,and Cogle, C.R. RNA Domains in Mitochondrial Ribosomes; Disposition of RNA in the small subunit of Bovine Mitochondrial Ribosomes, Gordon Research Conference on Mitochondrial and Chloroplasts, Volterra, Italy, May 1-6, 1994.

Courtney, B.C. and O’Brien, T.W., Binding of Mitochondrial mRNA to Bovine Mitochondrial Ribosomes, Gordon Research Conference on Mitochondria and Chloroplasts, Volterra, Italy, May 1-6, 1994.

O’Brien, T.W., Faunce, W.H., Courtney,B.C., Anders, J., Liu, J., and Heck, R., Structure and Function of Mammalian Mitochondrial Ribosomes, International Conference on theTranslational Apparatus, Berlin, October 31-November 5, 1992.

Denslow, N.D., Arroor, A.R., O’Brien, T.W.,and Wahba, A.J., In Vitro and In Vivo Phosphorylation of the Guanine Nucleotide Exchange Factor, Cold Spring Harbor, New York, September9-13, 1992.

Faunce, W. and O’Brien, T.W., Chemical and Enzymatic Probing of the 12S RNA Structure in the Small Subunit of Bovine Mitochondrial Ribosomes, The FASEB J., 4: A2002, (1990).

Denslow, N.D., Anders, J.C., Courtney,B.C., Sonnega, C.E.A. and O’Brien, T.W., Role of Initiation Factors and Ribosomal Proteins in Mammalian Mitochondrial Gene Expression, Cold Spring Harbor Symposium on Translational Control, Cold Spring Harbor, New York, September 13-17, 1989.

Denslow, N.D., Anders, J.C., Sonnega, C.E.A. and O’Brien, T.W., Characterization of a Novel GTP Binding Site in Mammalian Mitochondrial Ribosomes, American Society for Microbiology Conference on Ribosomes, East Glacier Park, Montana,August 6-11, 1989.

O’Brien, T.W., Anders, J.C., and Denslow, N.D., Purification and Microsequence Analysis of a GTP-binding Protein from Mammalian Mitochondrial Ribosomes, American Society for Microbiology Conference on Ribosomes, East Glacier Park, Montana,August 6-11, 1989.

O’Brien, T.W., Anders, J.C., Denslow, N.D.and Pietromonaco, S., Distinctive Properties of 55S Animal Mitochondrial Ribosomes, American Society for Microbiology Conference on Ribosomes, East Glacier Park, Montana, August 6-11, 1989.