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Catherine
F. Clarke Professor of Biochemistry B.S. and Ph.D., University of California, Los Angeles |
| Phone:
(310) 825-0771 Fax: (310) 206-5213 E-mail:cathy@chem.ucla.edu |
UCLA Department
of Chemistry & Biochemistry |
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Research Overview Elucidating Q biosynthesis Q and aging These results suggest that clk-1 is essential for Q biosynthesis, and that the aging and developmental phenotypes previously described may be attributed to Q levels. Our recent studies indicate that both mean and maximum life span of wild-type nematodes fed Q-less diets is extended 60%. This life span extension is quite robust and is observed in all Age mutants tested so far, when transferred to the Q-less diet as adults. Our current studies are aimed towards defining the metabolic alterations resulting from dietary Q, and should help determine how diet/environment and genotype interact to change longevity. Based on the strong conservation of Q biosynthesis and function, our findings should be very relevant to aging in other organisms.
From my Group 2001-Present 44. Jonassen, T., Larsen, P. L. and Clarke, C. F. (2001) "A dietary source of coenzyme Q is essential for growth of long-lived Caenorhabditis elegans clk-1 mutants." Proc. Natl. Acad. Sci. U.S.A. 98, 421-426. 45. Do, T. Q., Hsu, A. Y., Jonassen, T., Lee, P. T., and Clarke, C. F. (2001) "A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abc1 mutants." J. Biol. Chem. 276, 18161-18168. 46. Belogrudov,
G. I., Lee, P. T., Jonassen, T., Hsu, A. Y., Gin, P., and Clarke,
C. F. (2001) "Yeast COQ4 encodes a mitochondrial protein required
for coenzyme Q biosynthesis." Arch. Biochem. Biophys. 392, 48-58. 49. Jonassen, T., Marbois, B. N., Faull, K. F., Clarke, C. F. and Larsen, P. L. (2002) "Development and fertility in C. elegans clk-1 mutants depends upon transport of dietary coenzyme Q8 to mitochondria." J. Biol. Chem. 277, 45020-45027. 50. Gin, P. Hsu, A.Y., Rothman, S., Jonassen, T., Lee, P.T., Tzagoloff, A. and Clarke, C.F. (2003) "The Saccharomyces cerevisiae COQ6 gene encodes a flavin dependent monooxygenase required for coenzyme Q biosynthesis." J. Biol. Chem. 278, 25308-25316. 51. Jonassen, T., Davis, D. E., Larsen, P. L., and Clarke, C. F. (2003) "Reproductive fitness and quinonecontent of C. elegans clk-1 mutants fed coenzyme Q isoforms of varying length." J. Biol. Chem. 278, 51735-51742. 52. Baba, S.W., Belogrudov,
G.I., Lee, J.C., Lee, P.T., Strahan, J., Shepherd, J.N., Clarke,
C.F. (2004) "Yeast coq5 C-methyltransferase is required
for stability of other polypeptides involved in coenzyme q biosynthesis."
J. Biol Chem. Mar 12;279(11):10052-9.
54. Hsieh, E. J., Dinoso, J. B., and Clarke, C. F. (2004) "A tRNA-TRP gene mediates the suppression of cbs2-223 previously attributed to ABC1/COQ8." Biochem. Biophys. Res. Commun. 317, 648-653. 55. Padilla, S., Jonassen, T., Jimenez-Hidalgo, M. J., Fernandez-Ayala, D. J. M., Lopez-Lluch, G. M., Marbois, B., Navas, P., Clarke, C. F. and Santos-Ocana, C. (2004) "Demethoxy-Q, an intermediate of coenzyme Q biosynthesis, fails to support respiration in Saccharomyces cervisiase and lacks antioxidant activity". J. Biol. Chem. 279, 25995-26004. 56. Dyall, S.D., Yan, W., Delgadillo-Correa, M.G., Lunceford, A., Loo, J.A., Clarke, C.F., Johnson, P.J. (2004) "Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex." Nature. Oct 28;431(7012):1103-7. 57. Gin, P., Clarke, C.F. (2004) "Genetic evidence for a multi-subunit complex in coenzyme Q biosynthesis in yeast and the role of the Coq1 hexaprenyl diphosphate synthase." J Biol Chem. Jan 28;280(4):2676-81. 58. Marbois, B., Gin, P., Faull, K.F., Poon, W.W., Lee, P.T., Strahan, J., Shepherd, J.N., Clarke, C.F. (2005) "Coq3 and Coq4 define a polypeptide complex in yeast mitochondria for the biosynthesis of coenzyme Q." J Biol Chem. May 27;280(21):20231-8. 59. Johnson, A., Gin, P., Marbois, B.N., Hsieh, E.J., Wu, M., Barros, M.H., Clarke, C.F., Tzagoloff, A. (2005) "COQ9, a New Gene Required for the Biosynthesis of Coenzyme Q in Saccharomyces cerevisiae." J Biol Chem. Sep 9;280(36):31397-404. 60. Barros, M. H., Johnson, A., Gin, P., Marbois, B. N., Clarke, C. F. and Tzagoloff, A. (2005) “The Saccharomyces cerevisiae COQ10 gene encodes a START domain protein required for function of coenzyme Q in respiration.” J. Biol. Chem. 280, 42627-42635. 61. Tran, U. C., Marbois, B., Gin, P., Gulmezian, M., Jonassen, T., and Clarke, C. F. (2006) “Complementation of Saccharomyces cerevisiae coq7 mutants by mitochondrial targeting of the Escherichia coli UbiF polypeptide: two functions of yeast Coq7 polypeptide in coenzyme Q biosynthesis.” J. Biol. Chem. 281, 16401-16409. 62. Gulmezian, M., Zhang, H., Javor, G. T., and Clarke, C. F. (2006) “Genetic Evidence for an interaction of the UbiG O-methyltransferase with UbiX in Escherichia coli coenzyme Q biosynthesis.” J. Bacteriol. 188, 6435-6439. 63. Hsieh, E. J., Gin, P., Gulmezian, M., Tran, U. C., Saiki, R., Marbois, B. N. and Clarke, C. F. (2007) “Saccharomyces cerevisiae Coq9 polypeptide is a subunit of the mitochondrial coenzyme Q
biosynthetic complex.” Arch. Biochem. Biophys. 463, 19 -26. 69.
Saiki R, Lunceford AL, Shi Y, Marbois B, King R, Pachuski J, Kawamukai M, Gasser DL, Clarke CF. (2008) "Coenzyme Q10 Supplementation Rescues Renal Disease in Pdss2kd/kd mice with mutations in Prenyldiphosphate synthase subunit 2." 70. Do TQ, Moshkani S, Castillo P, Anunta S, Pogosyan A, Cheung A, Marbois B, Faull KF, Ernst W, Chiang SM, Fujii G, Clarke CF, Foster K, Porter E. (2008) "Lipids including cholesteryl linoleate and cholesteryl arachidonate contribute to the inherent antibacterial activity of human nasal fluid." J Immunol. Sep 15;181(6):4177-87. 71. Marbois, B., Gin, P., Gulmezian, M., and Clarke, C. F. (2009) "The Yeast Coq4 polypeptide
organizes a mitochondrial protein complex essential for coenzyme Q biosynthesis.” Biochim.
Biophys. Acta Mol. Cell. Biol. Lipid. 1791, 69-75. 75. Lomenick, B., Hao, R., Jonai, N., Chin, R. M., Aghajan, M., Warburton, S., Wang, J., Wu, R. P., Gomez, F., Loo, J. A., Wohlschlegel, J. A., Vondriska, T. M., Pelletier, J., Herschman, H. R., Clardy, J., Clarke, C. F., and Huang, J. (2009) “Target identification using drug affinity responsive target stability (DARTS).” Proc. Natl. Acad. Sci. USA 106, 21984-21989. 78. Devarajan, A., Bourquard, N., Hama, S., Navab, M., Grijalva, V.R., Morvaridi, S., Clarke, C. F., Vergnes, L., Reue, K., Tieber, J. F., and Reddy, S. T. (2010) “Paraoxanase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis.” Antioxid Redox Signal 14, 341-351. PMCID: PMC In Process. 79. Hill, S., Hirano, K., Shmanai, V. V., Marbois, B. N., Vidovic, D., Bekish, A. V., Kay, B., Tse, V., Fine, J., Clarke, C. F., and Shchepinov, M. S., (2011) “Isotope-reinforced polyunsaturated fatty acids strongly protect yeast cells from oxidative stress.” Free Radical Biol. Med. 50, 130-138. PMCID: PMC In Process. 80. Xie, L. X., Hsieh, E. J., Watanabe, S., Allan, C. M., Chen, J. Y., Tran, U. C., and Clarke, C. F. (2011) “Expression of the human atypical kinase ADCK3 rescues coenzyme Q biosynthesis and phosphorylation of Coq polypeptides in yeast coq8 mutants.” Biochim. Biophys. Acta (2011) 1811, 348-360. PMCID: PMC In Process. 81. Heeringa, S. F., Chernin, G., Chaki, M., Zhou, W., Sloan, A. J., Ji, Z., Xie, L. X., Salviati, L., Hurd, T. W., Vega-Warner, V., Killen, P. D., Raphael Y., Ashraf, S., Ovunc, B., Schoeb, D. S., McLaughlin, H. M., Airik, R., Vlangos, C. N., Gbadegesin, R., Hinkes, B., Saisawat, P., Trevisson, E., Doimo, M., Casarin, A., Pertegato, V., Giorgi, G., Prokisch, H., Rötig, A., Antignac, C., Nurnberg, G., Becker, C., Wang, S., Ozaltin, F., Topaloglu, R., Bakkaloglu, A., Bakkaloglu, S. A., Müller, D., Beissert, A., Mir, S., Berdeli, A., Özen, S., Zenker, M., Verena Matejas, V., Ocana, C. S., Navas, P., Kusakabe, T., Kispert, A., Akman, S., Soliman, N. A., Krick, S., Mundel, P., Reiser J., Peter Nurnberg, P., Clarke, C. F., Wiggins, R. C., Faul, C., and Hildebrandt, F. (2011) “COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness.” J. Clin. Invest. (2011) 121, 2013-2024. PMCID: PMC In Process. 82. Falk, M. J., Polyak, E., Zhang, Z., Peng, M., King, R., Maltzman, J. S., Okwuego, E., Horyn, O., Nakamaru-Ogiso, E., Ostrovsky, J., Xie, L. X., Chen, J. Y., Marbois, B., Nissim, I., Clarke, C. F., Gasser, D. L. (2011) “Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice.” EMBO Mol. Med. 7, 410-427. PMCID: PMC In Process. 83. Rahman, S., Clarke, C. F., and Hirano, M. (2011) “176th ENMC International Workshop: Diagnosis and treatment of coenzyme Q10 deficiency”. Neuromuscular Disorders. In press. PMCID: PMC In Process 84. Pfeiffer, M., Kayser, E.B., Yang, X., Abramson, E., Kenaston, M. A., Lago, C. U., Lo, H.H., Sedensky, M. M., Lunceford, A., Clarke, C. F., Wu, S. J., McLeod, C., Finkel, T., Morgan, P., Mills, E. M. (2011) “Caenorhabditis elegans UCP4 controls complex II-mediated oxidative phosphorylation through succinate transport.” J. Biol. Chem. In press. 85. Clarke, C. F. (2011) “Coq6 hydroxylase: Unmasked and bypassed.” Chem. Biol. 18, 1069-1070. |
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Research
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B.S., University of California, Los Angeles |
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B.S., University of California, Los Angeles |
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B.S., University of California, Los Angeles
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B.S., Loyola Marymount University, Los Angeles |
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B.S., University of California, Los Angeles |
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Quynh Pham UCLA Biochemistry |
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Former
Lab Members
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Updates?
We'd like to know! E-mail cathy@chem.ucla.edu
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Researchers |
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| Dr. Grigory Belogrudov | Department of Physiology, UCLA School of Medicine |
Research Associate, University of Illinois Champagne-Urbana |
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Research Associate, University of Rutgers |
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| Dr. Pam Larsen | University of Texas Health Sciences Center at San Antonio, Dept. of Cellular and Structural Biology |
Postdoctoral Fellows |
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B.S. & Ph.D., Lund University |
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B.A., M.S., & Ph.D. University of Shimane, Research Scientist, Funakoshi, Tokyo, Japan |
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Ph.D. Students |
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| Dr. Thai Do |
B.S., Ph.D.,UCLA, Project Scientist, Molecular Express, Rancho Dominguez, CA |
| Dr. Peter Gin | B.S., Ph.D. 2005, UCLA - Postdoc. Researcher - Dr. Stephen Young, Dept. of Medicne, UCLA |
| Dr. Melissa Gulmezian | B.A., University of California, Irvine; Ph.D., University of California, Los Angeles 2006; Scientist, Allergan, Irvine, CA |
| Dr. Edward Hsieh | Ph.D. 2006, UCLA - Research Faculty, Univ. of Washington, Seattle |
| Dr. Tanya Kruse | B.S., Ph.D., UCLA - Project Scientist, Baxter, Los Angeles, CA |
| B.S., Brigham Young University; Ph.D., University of California, Los Angeles 2008; J.D., UC Davis, Patent Attorney, Cooley LLP, Washington, D.C. | |
| Dr. Wayne Poon |
B.S., Ph.D. UCLA - Research Faculty, University of California, Irvine |
| Dr. UyenPhuong C. Tran | B.S., UCLA, Ph.D., University of California, Los Angeles 2007; Postdoctoral Fellow, UC San Diego |
| Master Students | |
| Suzie Ward Baba | |
| Diana Davis | B.S., North Carolina State University |
| Edouard Debonneuil | M.S., Computational Biology, University of California, Los Angeles |
| Shota Watanabe | B.S., University of California, Los Angeles, currently at the University of Hawaii Medical School |
| Undergraduate Students | |
| Jia Yan Chen | Class of 2011 - UCLA Biochemistry |
| Samuel Choi | Class of 2010 - UCLA Biochemistry |
| Peter Dang | Class of 2006 - UCLA Biochemistry, currently a Masters student at the UCLA School of Dentistry |
| Class of 2001 - UCLA Biochemistry, currently a postdoc at the University of Washington, Seattle | |
| Shauna Hill | B.S., Biochemistry, University of California, Los Angeles, currently a graduate student at The University of Texas Health Science Center at San Antonio |
| Kathleen Hirano | Class of 2009 - UCLA Biochemistry, currently a graduate student at UC Berkeley |
| Kyle Hyman | Class of 2008 - UCLA Biochemistry |
| Ziming Ji | Class of 2010 - BS Biophysics, University of California, Los Angeles |
| Bradley Kay | Class of 2011 - UCLA Biochemistry |
| Laura Lee | Class of 2010 - California State University, Fullerton |
| B.S., M.S., UCLA Biochemistry | |
| Amjad Nazzal | Current Biochemistry major, University of California, Los Angeles |
| Tin Mai | Class of 2009 - UCLA Biochemistry |
| Class of 2001 - UCLA Biochemistry | |
| An Pham | Class of 2010 - UCLA Biochemistry |
| Yuchen Shi | Class of 2008 - UCLA Biochemistry |
| Aye Win Tin | Class of 2011 - UCLA Biochemistry |
| Ruiwen Wang | Class of 2010 - UCLA Biochemistry |
| Summer Interns | |
| Jonathan Fine | Pali High 2011 |
| Eva Morozko | Class of 2012 - Seton Hall University, B.S. in Biochemistry |
| Jeffery Roth | Class of 2010 - Beverly Hills High |
Updated 10/14/11