Cathy Clarke

Catherine F. Clarke
Department of Chemistry and Biochemistry, UCLA

Professor of Biochemistry B.S. and Ph.D., University of California, Los Angeles

Phone: (310) 825-0771
Fax: (310) 206-5213

UCLA Department of Chemistry & Biochemistry
5072B Young Hall
Box 951569 (post)
607 Charles E. Young Drive East (courier)
Los Angeles, CA 90095-1569

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   Research Summary

Introduction – Ubiquinone (coenzyme Q or Q) functions in cells as a redox-active coenzyme of mitochondrial and plasma membrane electron transport, as well as an essential lipid soluble antioxidant. Human dietary supplementation with Q appears to have beneficial effects in slowing the progression of neuro- and muscle-degenerative diseases. However, Q is also involved in generating reactive oxygen species, through the adventitious reduction of dioxygen to superoxide by the ubisemiquinone radical, normally generated during mitochondrial electron transport. Thus, it is not clear how dietary supplementation with Q impacts the Dr. Jekyll/Mr. Hyde aspects of Q function. Cells are capable of synthesizing Q, but much remains to be learned about the sites of its synthesis, mechanisms of inter- and intra-cellular transport, and the regulation and enzymology of its biosynthesis. Research in my laboratory identified eight of the eleven polypeptides required for Q biosynthesis. The goals of my research are to characterize the Coq polypeptides responsible for production of Q and to determine how their activity can be modulated for optimal health.

Research Overview -

(1) We discovered a new Q biosynthetic pathway and showed that yeast are able to synthesize Q from a new aromatic ring precursor, para-aminobenzoic acid (pABA) [77]. This pathway operates in addition to the classic Q biosynthetic pathway that emanates from 4-hydroxybenzoic acid (4HB). We suggest a mechanism where Schiff base mediated deimination forms DMQ6 quinone, thereby eliminating the nitrogen contributed by pABA. This scheme results in the convergence of the 4HB and pABA pathways in eukaryotic Q biosynthesis and has implications regarding the action of pABA-based antifolates. This work is funded by a grant from NSF.

(2) The findings we made in the yeast model have shed much light on diseases resulting from Q deficiency [82, 85]. We showed that human Coq8 and Coq6 polypeptide homologues function to rescue the respective yeast coq mutants [80, 81]. We discovered that yeast Coq8p, and its human homologue ADCK3 function in the phosphorylation of Coq3p, Coq5p, and Coq7p [80]. The kinase function of Coq8p is proposed to be important in the maintenance or formation of a high molecular mass Coq polypeptide complex, which is required for Q biosynthesis.

(3) Over-expression of Coq8p in many of the yeast coq null mutants restores steady state levels of Coq polypeptides. This has been a particularly important discovery, because the yeast coq null mutants (coq3-coq9) previously accumulated the same early Q-intermediate. Coq8 over-expression has enabled us to detect late-stage Q-intermediates that were previously elusive [86]. Finally, we used synthetic analogues of 4-hydroxybenzoic acid to bypass deficient biosynthetic steps and showed that 2,4-dihydroxybenzoic acid is able to restore Q6 biosynthesis and respiratory growth in a coq7 null mutant over-expressing Coq8. The over-expression of Coq8 and the use of analogues of 4-HB represent new tools to elucidate the Q biosynthetic pathway. These recent discoveries are depicted in Figure 1.

Figure 1

Figure 1. S. cerevisiae Q6 biosynthetic pathway: accumulation of Q6 biosynthetic intermediates caused by the over-expression of Coq8 in Dcoq strains. The classic Q biosynthetic pathway is shown in path 1 emanating from 4-hydroxybenzoic acid (4-HB). Coq1 (not shown) synthesizes the hexaprenyl-diphosphate tail which is transferred by Coq2 to 4-HB to form 3-hexaprenyl-4-hydroxybenzoic acid (HHB).  R represents the hexaprenyl tail present in all intermediates from HHB to Q6. Alternatively, path 2 shows para-aminobenzoic acid (pABA) is prenylated by Coq2 to form 3-hexaprenyl-4-aminobenzoic acid (HAB). Both HHB and HAB are early Q-intermediates, readily detected in each of the coq null strains (Dcoq3-Dcoq9). The numbering of the aromatic carbon atoms used throughout this study is shown on the reduced form of Q6, Q6H2. Coq8 over-expression in certain Dcoq strains leads to the accumulation of the following compounds: 4-AP, 3-hexaprenyl-4-aminophenol; 4-HP, 3-hexaprenyl-4-hydroxyphenol; HHAB, 3-hexaprenyl-4-amino-5-hydroxybenzoic acid; HMAB, 3-hexaprenyl-4-amino-5-methoxybenzoic acid; DDMQ6, the oxidized form of demethyl-demethoxy-Q6H2; IDMQ6, 4-imino-demethoxy-Q6; DMQ6H2, demethoxy-Q6H2. IDDMQ6H2, 2-demethyl-4-amino-demethoxy-Q6H2 and DHHB, 3-hexaprenyl-4,5-dihydroxybenzoic acid are shown but have not been detected in this study. Black dotted arrows (from path 2 to path 1) designate the replacement of the C4-amine with a C4-hydroxyl and correspond to the C4-deamination reaction. A putative mechanism to replace the C4-imino group with the C4-hydroxy group is shown in bracket in blue on IDMQ6 but could also occur on IDDMQ6 (not shown). 4-AP and 4-HP which are formed upon inhibition of the C5-hydroxylation catalyzed by Coq6 are shown in red. Analogues of 4-HB and pABA allowing the bypass of certain steps in Q biosynthesis are indicated in green. Steps defective in the Dcoq9 strain are designated with a red asterisk.

4) In collaboration with Retrotope, we have employed novel isotope-reinforced polyunsaturated fatty acids (PUFAs) that reveal the importance of Q as an essential antioxidant [79, 87]. Polyunsaturated fatty acids (PUFA) undergo autoxidation and generate reactive carbonyl compounds that are toxic to cells and associated with apoptotic cell death, age-related neurodegenerative diseases, and atherosclerosis. PUFA autoxidation is initiated by the abstraction of bis-allylic hydrogen atoms. Replacement of the bis-allylic hydrogen atoms with deuterium atoms (termed site-specific isotope-reinforcement) arrests PUFA autoxidation due to the isotope effect. We investigate the effects of different isotope-reinforced PUFAs and natural PUFAs on autoxidation kinetics, and on the viability of coenzyme Q-deficient Saccharomyces cerevisiae coq mutants and wild-type yeast subjected to copper stress. Cells treated with a C11-BODIPY fluorescent probe to monitor lipid oxidation products show that lipid peroxidation precedes the loss of viability due to H-PUFA toxicity. We show that replacement of just one bis-allylic hydrogen atom with deuterium is sufficient to arrest lipid autoxidation. In contrast, PUFA reinforced with two deuterium atoms at mono-allylic sites remain susceptible to autoxidation. Surprisingly, yeast treated with a mixture of approximately 20%:80% isotope-reinforced D-PUFA: natural H-PUFA are profoundly protected from lipid autoxidation-mediated cell killing. Our findings show that inclusion of only a small fraction of PUFA deuterated at the bis-allylic sites is sufficient to profoundly inhibit the chain reaction of non-deuterated PUFA. .

Figure 2

Fig. 2. Replacement of bis-allylic H atoms with deuterium (D) arrests autoxidation of PUFA. A theoretical chain reaction is depicted where a single initiation event producing a lipid peroxyl radical (denoted by –OO•) starts a chain reaction of lipid autoxidation that in the presence of O2, may continue indefinitely and produce many molecules of lipid peroxides; susceptible phospholipid molecules containing a PUFA acyl chain are designated by a red dot. The presence of 20% isotope-reinforced PUFA (denoted by a black dot) inhibit (or slow) chain propagation. Propagation is inhibited for PUFA neighboring the D-PUFA.


 Representative Publications

From my Group 1996-2000
From my Group 2001-2005

From my Group 2006-2010

From my Group 2011-Present

125.  Guile, M. D., Jain, A., Anderson, K. A., Clarke, C. F. (2023) “New Insights on the Uptake and Trafficking of Coenzyme Q.” Antioxidants 12, 1391.

124.  Wang, S., Jain, A., Novales, N. A., Nashner, A. N., Tran, F., Clarke, C. F. (2022) “Predicting and Understanding the Pathology of Single Nucleotide Variants in Human COQ Genes.” Antioxidants 11, 2308.

123.  Yang, M. L., Connolly, S. E., Gee, R. J., Lam, T. T., Kanyo, J., Peng, J., Guyer, P., Syed, F., Tse, J. M., CLarke, S. G., Clarke, C. F., James, E. A., Speake, C., Evans-Molina, C., Arvan, P., Herold, K. C., Wen, L., Mamula, M. J. (2022) “Carbonyl Posttranslational Modification Associated with Early-Onset Type 1 Diabetes Autoimmunity” Diabetes 71, 1979-1993.

122.  Latimer, S., Keene, S. A>, Stutts, L. R., Berger, A., Bernert, A. C., Soubeyrand, E., Wright, J., Clarke, C. F., Block, A. K., Colquhoun, T. A., Elowsky, C., Christensen, A., Wilson, M. A., Basset, G. J. (2021) “A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis” J Biol Chem 297, 101283.

121.  Ayer, A., Fazakerley, D. J., Suarna, C., Maghzal, G. J., Sheipouri, D., Lee, K. J., Bradley, M. C., Fernández-del-Río, L., Tumanov, S., Kong, S. M., van der Veen, J. N., Yang, A., Ho, J. W. K., Clarke, S. G., James, D. E., Dawes, I. W., Vance, D. E., Clarke, C. F., Jacobs, R. L., Stocker, R. (2021) “Genetic screening reveals phospholipid metabolism as a key regulator of the biosynthesis of the redox-active lipid coenzyme Q.” Redox Biol 46, 102127.

120.  Fernández-del-Río, L., Rodriguez-Lopez, S., Gutierrez-Casado, E., Gonzalez-Reyes, J. A., Clarke, C. F., Buron, M. I., and Villalba, J. M. (2021) “Regulation of hepatic coenzyme Q biosynthesis by dietary omega-3 polyunsaturated fatty acids.” Redox Biol 46, 102061.

119.  Fernández-del-Río, L., and Clarke, C. F. (2021) “Coenzyme Q Biosynthesis: An Update on the Origins of the Benzenoid Ring and Discovery of New Ring Precursors.” Metabolites 11, 385-401.

118.  Acoba, M. G., Alpergin, E. S. S., Renuse, S., Fernández-del-Río, L., Lu, Y. W., Khalimonchuk, O., Clarke, C. F., Pandey, A., Wolfgang, M. J., and Claypool, S. M. (2021) “The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism.” Cell Rep 34, 108869.

117.  Fernández-del-Río, L., Soubeyrand, E., Basset, G. J., and Clarke, C. F. (2020) “Metabolism of the Flavonol Kaempferol in Kidney Cells Liberates the B-ring to Enter Coenzyme Q Biosynthesis.” Molecules 25, 2955-2962.

116.  Awad, A. M., Nag, A., Pham, N. V. B., Bradley, M. C., Jabassini, N., Nathaniel, J., and Clarke, C. F. (2020) “Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae.” PLoS One 15, e0234192.

115.  Fernández-del-Río, L., Kelly, M. E., Contreras, J., Bradley, M. C., James, A. M., Murphy, M. P., Payne, G. S., and Clarke, C. F. (2020) “Genes and lipids that impact uptake and assimilation of exogenous coenzyme Q in Saccharomyces cerevisiae.” Free Radic Biol Med 154, 105-118.

114.  Widmeier, E., Yu, S., Nag, A., Chung, Y. W., Nakayama, M., Fernández-Del-Río, L., Hugo, H., Schapiro, D., Buerger, F., Choi, W. I., Helmstadter, M., Kim, J. W., Ryu, J. H., Lee, M. G., Clarke, C. F., Hildebrandt, F., and Gee, H. Y. (2020) “ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment.” J Am Soc Nephrol 31, 1191-1211.

113.  Bradley, M. C., Yang, K., Fernández-Del-Río, L., Ngo, J., Ayer, A., Tsui, H. S., Novales, N. A., Stocker, R., Shirihai, O. S., Barros, M. H., and Clarke, C. F. (2020) “COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10.” J Biol Chem 295, 6023-6042.

112.  Bernert, A. C., Jacobs, E. J., Reinl, S. R., Choi, C. C. Y., Roberts Buceta, P. M., Culver, J. C., Goodspeed, C. R., Bradley, M. C., Clarke, C. F., Basset, G. J., and Shepherd, J. N. (2019) “Recombinant RquA catalyzes the in vivo conversion of ubiquinone to rhodoquinone in Escherichia coli and Saccharomyces cerevisiae.” Biochim Biophys Acta Mol Cell Biol Lipids 1864, 1226-1234.

111.  Tsui, H. S., Pham, N. V. B., Amer, B. R., Bradley, M. C., Gosschalk, J. E., Gallagher-Jones, M., Ibarra, H., Clubb, R. T., Blaby-Haas, C. E., and Clarke, C. F. (2019) “Human COQ10A and COQ10B are distinct lipid-binding START domain proteins required for coenzyme Q function.” Journal of lipid research 60, 1293-1310.

110.  Eisenberg-Bord, M., Tsui, H. S., Antunes, D., Fernández-Del-Río, L., Bradley, M. C., Dunn, C. D., Nguyen, T. P. T., Rapaport, D., Clarke, C. F., and Schuldiner, M. (2019) “The Endoplasmic Reticulum-Mitochondria Encounter Structure Complex Coordinates Coenzyme Q Biosynthesis.” Contact (Thousand Oaks) 2, 1-14.

109.  Widmeier, E., Airik, M., Hugo, H., Schapiro, D., Wedel, J., Ghosh, C. C., Nakayama, M., Schneider, R., Awad, A. M., Nag, A., Cho, J., Schueler, M., Clarke, C. F., Airik, R., and Hildebrandt, F. (2019) “Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Coq6 Knockout Mice.” J Am Soc Nephrol 30, 393-405.

108.  Awad, A. M., Bradley, M. C., Fernández-Del-Río, L., Nag, A., Tsui, H. S., and Clarke, C. F. (2018) “Coenzyme Q10 deficiencies: pathways in yeast and humans.“ Essays Biochem 62, 361-376.

107.  Awad, A. M., Venkataramanan, S., Nag, A., Galivanche, A. R., Bradley, M. C., Neves, L., Douglass, S., Clarke, C. F., Johnson T. L. (2017) “Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast.” J Biol Chem 292, 14851-14866.

106.  He, C. H., Black, D. S., Allan, C. M., Meunier, B., Rahman, S., Clarke, C. F. (2017) “Human COQ9 rescues a coq9 yeast mutant by enhancing coenzyme Q biosynthesis from 4-hydroxybenzoic acid and stabilizing the CoQ synthome.” Frontiers in Physiology 8, 463.

105.  Fernández-del-Río, L., Nag, A., Gutiérrez Casado, E., Ariza, J., Awad, A. M., Joseph, A. I., Kwon, O., Verdin, E., de Cabo, R., Schneider, C., Torres, J. Z., Burón, M. I., Clarke, C. F., Villalba, J. M. (2017) “Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.” Free Rad Biol Med 110, 176-187.

104. Clarke CF, Allan CM. (2015) "Biochemistry: Unexpected role for vitamin B2." Nature. 2015 Jun 25;522(7557):427-8. doi: 10.1038/nature14536. Epub 2015 Jun 17. No abstract available. PMID: 26083748

103. He CH, Black DS, Nguyen TP, Wang C, Srinivasan C, Clarke CF. (2015) "Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid." Biochim Biophys Acta. 2015 Sep;1851(9):1227-39. doi: 10.1016/j.bbalip.2015.05.003. Epub 2015 May 23. PMID: 26008578

102. Xie LX, Williams KJ, He CH, Weng E, Khong S, Rose TE, Kwon O, Bensinger SJ, Marbois BN, Clarke CF. (2015) "Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis." J Lipid Res. 2015 Apr;56(4):909-19. doi: 10.1194/jlr.M057919. Epub 2015 Feb 14. PMID: 25681964

101. Allan CM, Awad AM, Johnson JS, Shirasaki DI, Wang C, Blaby-Haas CE, Merchant SS, Loo JA, Clarke CF. (2015) "Identification of Coq11, a new coenzyme Q biosynthetic protein in the CoQ-synthome in Saccharomyces cerevisiae." J Biol Chem. 2015 Mar 20;290(12):7517-34. doi: 10.1074/jbc.M114.633131. Epub 2015 Jan 28. PMID: 25631044

100. Andreyev AY, Tsui HS, Milne GL, Shmanai VV, Bekish AV, Fomich MA, Pham MN, Nong Y, Murphy AN, Clarke CF, Shchepinov MS. (2015) "Isotope-reinforced polyunsaturated fatty acids protect mitochondria from oxidative stress." Free Radic Biol Med. 2015 May;82:63-72. doi: 10.1016/j.freeradbiomed.2014.12.023. Epub 2015 Jan 8. PMID: 25578654

99. Nguyen, T. P. T., Casarin, A., Desbats, M. A., Doimo, M., Trevisson, E., Santos-Ocana, C., Navas, P., Clarke, C. F., and Salviati, L. (2014) "Molecular characterization of the human COQ5 C-methyltransferase in Coenzyme Q10 biosynthesis. "Biochim Biophys Acta. 2014 Nov;1841(11):1628-38. doi: 10.1016/j.bbalip.2014.08.007. Epub 2014 Aug 23. PMID: 25152161

98. Shchepinov, M. S., Roginsky, V. A., Brenna, J. T., Molinari, R. J., To, R., Tsui, H., Clarke, C. F., and Manning-Bog, A. B. (2014) "Chapter 31 - Deuterium protection of polyunsaturated fatty acids against lipid peroxidation: A novel approach to mitigating mitochondrial neurological diseases". In Omega-3 Fatty Acids in Brain and Neurological Health (Watson, ed.) pp. 373-383.

97. Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V.S., Monsalve, G.C., Hu, E., Whelan, S.A., Wang, J.X., Jung, G., Solis, G.M., Fazlollahi, F., Kaweeteerawat, C., Quach, A., Nili, M., Krall, A.S., Godwin, H.A., Chang, H.R., Faull, K.F., Guo, F., Jiang, M., Trauger, S.A., Saghatelian, A., Braas, D., Christofk, H.R, Clarke, C.F., Teitell, M.A., Petrascheck, M., Reue, K., Jung, M.E., Frand, A.R., Huang, J. "The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR." Nature. 2014 Jun 19;510(7505):397-401. PMCID: In Process.

96. Clarke CF, Rowat AC, Gober JW. "Osmotic stress: Is CoQ a membrane stabilizer?". Nat Chem Biol. 2014 Apr;10(4):242-3. PMCID: In Process

95. He, C.H., Xie, L. X., Allan, C. M., Tran, U. C., and Clarke, C. F. (2014) "Coenzyme Q supplementation or over-expression of the yeast Coq8 kinase stabilizes multi-subunit Coq polypeptides complexes in yeast coq null mutants." Biochim Biophys Acta 1841, 630-644. PMCID: PMC3959571.

94. Lamberson, C. R., Xu, L., Muchalski, H., Montenegro-Burke, J. R., Shmanai, V. V., Bekish, A. V., McLean, J. A., Clarke, C. F., Shchepinov, M. S., and Porter, N. A. (2014) "Unusual kinetic isotope effects of deuterium reinforced polyunsaturated fatty acids in tocopherol mediated free radical chain oxidations." J. Amer. Chem. Soc. 136, 838-841. PMCID: In Process.

93. Ashraf, S., Gee, H. Y., Woerner, S., Xie, L. X., Vega-Warner, V., Svjetlana, L., Fang, H., Song, X., Cattran, D. C., Avila-Casado, C., Paterson, A. D., Nitschke, P., Bole-Feysot, C., Cochat, P., Esteve-Rudd, J., Haberberger, B., Allen, S. J., Zhou, W., Airik, R., Otto, E. A., Barua, M., Al-Hamed, M. H., Kari, J. A., Bockenhauer, D., Kleta, R., El Desoky, S., Hacihamdioglu, D. O., Gok, F., Washburn, J., Wiggins, R. C., Choi, M., Lifton, R. P., Levy, S., Han, Z., Salviati, L., Prokisch, H., Williams, D. S., Pollak, M., Clarke, C. F., Pei, Y., Antignac, C., and Hildebrandt, F. (2013) "ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption." J. Clin. Invest. 123, 5179-5189. PMCID: PMC3859425.

92. Gasser, D. L., Winkler, C. A., Peng M., Ping, A., McKenzie, L. M., Kirk, G. D., Shi, Y., Xie, L. X., Marbois, B. N., Clarke, C. F., and Kopp, J. B. (2013) "Focal Segmental Glomerulosclerosis is associated with a PDSS2 haplotype and independently, with a decreased content of coenzyme Q10." Amer. J. Physiol. Renal Physiol. Am J Physiol Renal Physiol. Oct; 305(8):F1228-38. PMCID: PMC3798722.

91. Allan, C. M., Hill, S., Morvaridi, S., Saiki, R., Johnson, J. S., Liau, W-S., Hirano, K., Kawashima, T., Ziming, J., Loo, J. A., Shepherd, J. N., and Clarke, C. F. (2013) "A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae". Biochim. Biophys. Acta 1831, 776-791. PMCID: PMC3909687.

90. Gomez, F., Monsalve, G. C., Tse, V., Saiki, R., Weng, E., Lee, L., Srinivasan, C., Frand, A. R., and Clarke, C. F. (2012) "Delayed accumulation of intestinal coliform bacteria enhance life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli." BMC Microbiol. 12, 300. PMCID: PMC3548685.

89. Nguyen, T. P. T., Clarke, C. F. (2012) "Folate status of gut microbiome affects Caenorhabditis elegans lifespan". BMC Biology 10, 66 PMCID: PMC3409036.

88. Gomez, F., Saiki, R., Chin, R., Srinivasan, C., and Clarke, C. F. (2012) "Restoring de novo coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous coenzyme Q supplementation". Gene 506, 106-116. PMCID: PMC3437764.

87. Hill, S., Lamberson, C. R., Libin X., To, R., Tsui, H. S., Shmanai, V. V., Bekish, A. V., Awad, A. M., Marbois, B. N., Cantor, C. R., Porter, N. A., Clarke, C. F., and Shchepinov, M. S. (2012) "Small amounts of isotope-reinforced polyunsaturated fatty acids suppress lipid autoxidation." Free Rad. Biol. Med. 53, 893-906. PMCID: PMC3437768.

86. Xie, L. X., Ozeir, M., Tang, J. Y., Chen, J. Y., Jaquinod, S-K., Fontecave, M, Clarke, C. F., and Pierrel, F. (2012) "Over-expression of the Coq8 kinase in Saccharomyces cerevisiae coq null mutants allows for accumulation of diagnostic intermediates of the coenzyme Q6 biosynthetic pathway." J. Biol. Chem. 287, 23571-23581. PMCID: PMC3390632.

85. Rahman, S., Clarke, C. F., and Hirano, M. (2011) “176th ENMC International Workshop: Diagnosis and treatment of coenzyme Q10 deficiency”. Neuromuscular Disorders. 22, 76-86. PMCID: PMC3222743. REVIEW ARTICLE

84. Clarke, C. F. (2011) “Coq6 hydroxylase: Unmasked and bypassed.” Chem. Biol. 18, 1069-1070. PMCID:PMC3245979. INVITED COMMENTARY

83. 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. 286, 37712-37720. PMCID:PMC3199514.

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: PMC3394513.

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: PMC3083770.

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: PMC3075350.

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: PMC3014413.


 Current Members of Clarke Lab
Ph.D. Students
Kelsey Feustel

Kelsey Feustel Gage

B.S., Westmont College

Kelsey's work focuses on functionally characterizing Coq11, an atypical short-chain dehydrogenase/reductase (SDR) that modulates coenzyme Q (CoQ) biosynthesis in Saccharomyces cerevisiae, through the use of mutagenesis studies carried out using CRISPR-Cas9-mediated genome editing.

Michael Guile

Michael Guile

B.S., Missouri State University

Michael uses classical biochemical and molecular biology techniques to investigate mechanisms of cellular uptake of exogenous CoQ and to elucidate the pathway of intracellular trafficking into respiratory complexes within the mitochondria. Characterizing these processes is important to understanding the complex roles of CoQ and improving therapeutics with CoQ in human health and disease. In his free time, he likes to knit and sew clothing.

Alexa Novales

Noelle Alexa Novales

B.S., California State University, Long Beach

Alexa's research interests include elucidating the influence of membrane contact sites on the regulation of CoQ biosynthesis, and utilizing synthetic tethering constructs as a tool to study crosstalk between mitochondria and the ER. In addition to research, she enjoys teaching various levels of chemistry, and is also completing her Graduate Certificate in Writing Pedagogy at UCLA. Outside of the lab and the classroom, Alexa enjoys baking alongside her rescue pitbull, Rambo!

Cindy Wang

Sining (Cindy) Wang

B.S., University of California, Los Angeles

Cindy is a joint student between the labs of Profs. Catherine Clarke and Steven Clarke. Her work focuses on elucidating the molecular mechanism and structure-function relationship of COQ5, a C-methyltransferase involved in coenzyme Q biosynthesis, in the context of pathogenic single nucleotide variants in humans.

Undergraduate Students
Kyle Anderson

Kyle Anderson

Biochemistry, University of California, Los Angeles

Kyle is a second-year biochemistry major assisting in the investigation of autophagy-mediated exogenous CoQ uptake in Saccharomyces cerevisiae. He joined the Clarke lab in the Fall of 2022 and has been further integrating himself into the team ever since. In his free time, he is either running, playing guitar, or attending seminars, and he intends to pursue a Master's degree after graduation from UCLA.

Celeste Medina-Seymoure

Celeste Medina-Seymoure

Biochemistry, University of California, Los Angeles

Celeste is a third year undergraduate student majoring in Biochemistry.

Group Photo
Group Photo 2017

Former Lab Members
Updates? We'd like to know! E-mail
Dr. Grigory Belogrudov Department of Physiology, UCLA School of Medicine
Dr. Deborah Berthold Research Associate, University of Illinois Champagne-Urbana
Dr. Jenna Hutton Research Associate, University of Rutgers
Dr. Pam Larsen University of Texas Health Sciences Center at San Antonio, Dept. of Cellular & Structural Biology
Dr. Beth Marbois Research Scientist, GSK Vaccines, Rockville, MD
Postdoctoral Fellows
Dr. Lucía Fernández del Río B.A., M.S., & Ph.D. Universidad de Córdoba - Assistant Director, Mitochondria and Metabolism Core Facility, UCLA
Dr. Susan Morvaridi B.S. & Ph.D., Lund University, Research Scientist, UCLA School of Medicine
Dr. Ryoichi Saiki B.A., M.S., & Ph.D. University of Shimane - Research Scientist, Funakoshi, Tokyo, Japan
Ph.D. Students
Dr. Chris Allan B.S., 2007; Ph.D., 2014, UCLA - Postdoctoral Fellow, UCLA Department of Medicine
Dr. Agape Awad B.S., 2013; Ph.D., 2018, UCLA - Research Manager, Amgen
Dr. Michelle Bradley B.S., 2015, Colgate University; Ph.D., 2020, UCLA - Patent Agent, Morrison & Foerster LLP
Dr. Thai Do B.S.; Ph.D., UCLA - Project Scientist, Molecular Express, Rancho Dominguez, CA
Dr. Peter Gin B.S.; Ph.D., 2005, UCLA - Project Scientist, Kite Pharma, Santa Monica, CA
Dr. Fernando Gomez B.S.; Ph.D., 2012, UCLA - Director of Biological Instruction
Dr. Melissa Gulmezian B.A., UC Irvine; Ph.D., 2006, UCLA - Scientist, Allergan, Irvine, CA
Dr. Edward Hsieh Ph.D., 2006, UCLA - Research Scientist, Merck Laboratories, San Francisco
Dr. Cuiwen He  B.S., 2010; Ph.D., 2015, UCLA - Postdoctoral Fellow, UCLA Department of Medicine
Dr. Tanya Kruse B.S.; Ph.D., UCLA - Project Scientist, Baxalta, Los Angeles, CA

Dr. Adam Lunceford

B.S., Brigham Young University; Ph.D., 2008, UCLA; J.D., UC Davis - Patent Attorney, Bayer Crop Science. West Sacramento, CA
Dr. Anish Nag B.S., 2013, Indian Institute of Technology, Kharagpur; Ph.D., 2019, UCLA - Senior Scientist, Amgen
Dr. Theresa Nguyen B.S., Loyola Marymount University, Los Angeles, CA; Ph.D., 2014, UCLA - Asst. Prof. Dept. of Chemistry, Loyola Marymount Univesrity, Baltimore MD
Dr. Wayne Poon B.S.; Ph.D., UCLA - Research Faculty, UC Irvine
Dr. UyenPhuong C. Tran B.S., UCLA; Ph.D., 2007, UCLA - Research Scientist, Department of Biological Chemistry, UC Irvine
Dr. Hui (Sue) Tsui B.A. & M.S., 2013; Ph.D., 2019, UCLA - Senior Scientist, AbbVie Bioresearch Center
Dr. Letian Xie B.S., 2008; Ph.D., 2014, UCLA - Instructor, Evergreen College
Master Students
Suzie Ward Baba B.S.
Diana Davis B.S., North Carolina State University; M.S., UCLA
Edouard Debonneuil M.S., Computational Biology, UCLA
Christopher Kampmeyer B.S., 2014, U Penn; M.S., 2016, UCLA - Scientific Consultant, Exponent
Barry Lee M.S., Biochemistry, UCLA
Kelly Quinn B.S., 2013, UC Berkeley; M.S., 2015, UCLA - currently attending the University of Hawaii Medical School
Shota Watanabe B.S., M.S., UCLA, currently attending the University of Hawaii Medical School
Undergraduate Students
Agape Awad Class of 2013, UCLA Biochemistry - Ph.D. candidate UCLA Biochemistry & Molecular Biology
Dylan Black Class of 2016, UCLA Biophysics - Ph.D. candidate Stanford University Electrical Engineering
Jia Yan Chen Class of 2011 , UCLA Biochemistry
Samuel Choi Class of 2010, UCLA Biochemistry
Peter Dang Class of 2006, UCLA Biochemistry

Jason Dinoso

Class of 2001, UCLA Biochemistry - postdoc at the University of Washington, Seattle
Shauna Hill B.S., Biochemistry, UCLA - graduate student at The University of Texas Health Science Center at San Antonio
Kathleen Hirano Class of 2009, UCLA Biochemistry - graduate student at UC Berkeley
Alice Hsu Class of 2015, UCLA Biochemistry - Ph.D. Candidate Bioengineering, Cal Tech
Abdiasis Hussein Class of 2014, UCLA Biochemistry - Ph.D. Candidate Biochemistry University of Washington
Carissa Huynh Class of 2015, UCLA Biochemistry - Staff Researcher, Cedar Sinai Hospital
Kyle Hyman Class of 2008, UCLA Biochemistry
Hope Ibarra Class of 2017, UCLA Biochemistry - Thermo Fisher employee
Nora Jabassini Class of 2020, UCLA Biochemistry - Neurology research associate at UC San Francisco
Akash Jain Current Biochemistry major, UCLA - Undergraduate research assistant at Nicolaos Palaskas Lab
Tina Javanbakht     Class of 2018, UCLA
Ziming Ji Class of 2010,  UCLA Biophysics
Jarrett Johnson B.S., Biochemistry, UCLA - graduate student in Chemical Biology at U Michigan
Bradley Kay Class of 2011, UCLA Biochemistry
Miranda Kelly Class of 2020, UCLA Biochemistry - graduate student at UC Irvine Cellular & Molecular Biosciences
HeiTong (Nikki) Lam Class of 2016, UCLA Biochemistry - Medical School Student at University of Ohio
Laura Lee Class of 2010, California State University, Fullerton

Nico Lee

B.S., M.S., UCLA Biochemistry

Mark Lui

Class of 2012, UCLA Biochemistry
Tin Mai Class of 2009, UCLA Biochemistry
Amjad Nazzal Current Biochemistry major, UCLA
Audrey N. Nashner Current Biochemistry major, UCLA - Undergraduate research assistant at Anne Andrews Lab
Yvonne Nong Class of 2014, UCLA Biochemistry - Certified Personal Trainer, Los Angeles
Sabine Paterson Class of 2001, UCLA Biochemistry
An Pham Class of 2010, UCLA Biochemistry
Minhhan Pham Class of 2014, UCLA Biochemistry
Nguyen Pham Class of 2017, UCLA Biochemistry
Quynh Pham Class of 2013, UCLA Biochemistry
Thuy Anh Pham Class of 2013, UCLA Biochemistry
Bryce Raja Class of 2019, UCLA Biochemistry
Tomer Schwartz Class of 2012, UCLA Biochemistry
Yuchen Shi Class of 2008, UCLA Biochemistry
Jennifer Tang Class of 2012, UCLA Biochemistry
Aye Win Tin Class of 2011, UCLA Biochemistry
Randy To Class of 2012, UCLA Biochemistry
Fiona Tran Class of 2021, UCLA Biochemistry, minor in Biomedical Engineering - PharmD student at UC San Francisco
Vincent Tse Class of 2012, UCLA Mol. Cell. Dev. Biol.
Emily Weng Class of 2014, UCLA Mol. Cell. Dev. Biol.
Ruiwen Wang Class of 2010, UCLA Biochemistry
Krista Yang Class of 2020, UCLA Biochemistry
Victoria Zheng Class of 2023, UCLA Biochemistry - PhD student at NYU Biology
Summer Interns
Jonathan Fine Class 2011, Pali High
Eva Morozko Class of 2012, Seton Hall University, B.S. in Biochemistry
Jeffery Roth Class of 2010, Beverly Hills High School


Updated August 18, 2015