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Review

Biosynthesis of coenzyme Q in eukaryotes

Pages 23-33 | Received 07 May 2015, Accepted 07 Jun 2015, Published online: 17 Jul 2015

References

  • Kawamukai M. Biosynthesis and bioproduction of coenzyme Q 10 by yeasts and other organisms. Biotechnol. Appl. Biochem. 2009;53:217–226.10.1042/BA20090035
  • Inaba K. Disulfide bond formation system in Escherichia coli. J. Biochem. (Tokyo). 2009;146:591–597.10.1093/jb/mvp102
  • Zhang M, Wakitani S, Hayashi K, Miki R, Kawamukai M. High production of sulfide in coenzyme Q deficient fission yeast. BioFactors. 2008;32:91–98.10.1002/biof.v32:1/4
  • Šimkovič M, Frerman FE. Alternative quinone substrates and inhibitors of human electron-transfer flavoprotein-ubiquinone oxidoreductase. Biochem. J. 2004;378:633–640.10.1042/BJ20031272
  • Lopez-Martin JM, Salviati L, Trevisson E, et al. Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis. Hum. Mol. Genet. 2007;16:1091–1097.10.1093/hmg/ddm058
  • Matsuo Y, Nishino K, Mizuno K, et al. Polypeptone induces Dramatic cell lysis in ura4 deletion mutants of fission yeast. PLoS ONE. 2013;8:e59887.10.1371/journal.pone.0059887
  • Okada K, Suzuki K, Kamiya Y, et al. Polyprenyl diphosphate synthase essentially defines the length of the side chain of ubiquinone. Biochim. Biophys. Acta. 1996;1302:217–223.10.1016/0005-2760(96)00064-1
  • Okada K, Kainou T, Matsuda H, Kawamukai M. Biological significance of the side chain length of ubiquinone in Saccharomyces cerevisiae. FEBS Lett. 1998;431:241–244.10.1016/S0014-5793(98)00753-4
  • Kawamukai M. Biosynthesis, bioproduction and novel roles of ubiquinone. J. Biosci. Bioeng. 2002;94:511–517.10.1016/S1389-1723(02)80188-8
  • Aussel L, Pierrel F, Loiseau L, Lombard M, Fontecave M, Barras F. Biosynthesis and physiology of coenzyme Q in bacteria. Biochim. Biophys. Acta. 2014;1837:1004–1011.10.1016/j.bbabio.2014.01.015
  • Meganathan R. Ubiquinone biosynthesis in microorganisms. FEMS Microbiol. Lett. 2001;203:131–139.
  • Tran UC, Clarke CF. Endogenous synthesis of coenzyme Q in eukaryotes. Mitochondrion. 2007;7:S62–S71.10.1016/j.mito.2007.03.007
  • Tzagoloff A, Dieckmann CL. PET genes of Saccharomyces cerevisiae. Microbiol. Rev. 1990;54:211–225.
  • Hajj Chehade M, Loiseau L, Lombard M, et al. ubil, a new gene in Escherichia coli coenzyme Q biosynthesis, is involved in aerobic C5-hydroxylation. J. Biol. Chem. 2013;288:20085–20092.10.1074/jbc.M113.480368
  • Hayashi K, Ogiyama Y, Yokomi K, Nakagawa T, Kaino T, Kawamukai M. Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants, and humans. PLoS ONE. 2014;9:e99038.10.1371/journal.pone.0099038
  • Gavilán ÁNgela, Asencio C, Cabello J, Rodríguez-Aguilera JC, Schnabel R, Navas P. C. elegans knockouts in ubiquinone biosynthesis genes result in different phenotypes during larval development. BioFactors. 2005;25:21–29.10.1002/biof.v25:1/4
  • Zhang M, Luo J, Ogiyama Y, Saiki R, Kawamukai M. Heteromer formation of a long-chain prenyl diphosphate synthase from fission yeast Dps1 and budding yeast Coq1. FEBS J. 2008;275:3653–3668.10.1111/j.1742-4658.2008.06510.x
  • Saiki R, Nagata A, Uchida N, Kainou T, Matsuda H, Kawamukai M. Fission yeast decaprenyl diphosphate synthase consists of Dps1 and the newly characterized Dlp1 protein in a novel heterotetrameric structure. Eur. J. Biochem. 2003;270:4113–4121.10.1046/j.1432-1033.2003.03804.x
  • Saiki R, Nagata A, Kainou T, Matsuda H, Kawamukai M. Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans. FEBS J. 2005;272:5606–5622.10.1111/ejb.2005.272.issue-21
  • Kainou T, Okada K, Suzuki K, Nakagawa T, Matsuda H, Kawamukai M. Dimer formation of octaprenyl-diphosphate synthase (IspB) is essential for chain length determination of ubiquinone. J. Biol. Chem. 2001;276:7876–7883.10.1074/jbc.M007472200
  • Okada K, Kainou T, Tanaka K, Nakagawa T, Matsuda H, Kawamukai M. Molecular cloning and mutational analysis of the ddsA gene encoding decaprenyl diphosphate synthase from Gluconobacter suboxydans. Eur. J. Biochem. 1998;255:52–59.10.1046/j.1432-1327.1998.2550052.x
  • Okada K, Kamiya Y, Zhu X, et al. Cloning of the sdsA gene encoding solanesyl diphosphate synthase from Rhodobacter capsulatus and its functional expression in Escherichia coli and Saccharomyces cerevisiae. J. Bacteriol. 1997;179:5992–5998.
  • Jun L, Saiki R, Tatsumi K, Nakagawa T, Kawamukai M. Identification and subcellular localization of two solanesyl diphosphate synthases from Arabidopsis thaliana. Plant Cell Physiol. 2004;45:1882–1888.10.1093/pcp/pch211
  • Ducluzeau AL, Wamboldt Y, Elowsky CG, Mackenzie SA, Schuurink RC, Basset GJ. Gene network reconstruction identifies the authentic trans-prenyl diphosphate synthase that makes the solanesyl moiety of ubiquinone-9 in Arabidopsis. Plant J. 2012;69:366–375.10.1111/tpj.2011.69.issue-2
  • Suzuki K, Okada K, Kamiya Y, et al. Analysis of the decaprenyl diphosphate synthase (dps) gene in fission yeast suggests a role of ubiquinone as an antioxidant. J. Biochem. (Tokyo). 1997;121:496–505.10.1093/oxfordjournals.jbchem.a021614
  • Cui TZ, Kaino T, Kawamukai M. A subunit of decaprenyl diphosphate synthase stabilizes octaprenyl diphosphate synthase in Escherichia coli by forming a high-molecular weight complex. FEBS Lett. 2010;584:652–656.10.1016/j.febslet.2009.12.029
  • Guo RT, Kuo CJ, Chou CC, et al. Crystal structure of octaprenyl pyrophosphate synthase from hyperthermophilic Thermotoga maritima and mechanism of product chain length determination. J. Biol. Chem. 2004;279:4903–4912.
  • Han X, Chen CC, Kuo CJ, et al. Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms. Proteins. 2015;83:37–45.10.1002/prot.v83.1
  • Saiki R, Lunceford AL, Shi Y, et al. Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2. Am. J. Physiol. Renal Physiol. 2008;295:F1535–F1544.10.1152/ajprenal.90445.2008
  • López LC, Schuelke M, Quinzii CM, et al. Leigh syndrome with nephropathy and CoQ10 Deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am. J. Hum. Genet. 2006;79:1125–1129.10.1086/510023
  • Mollet J, Giurgea I, Schlemmer D, et al. Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J. Clin. Invest. 2007;117:765–772.10.1172/JCI29089
  • Uchida N, Suzuki K, Saiki R, et al. Phenotypes of fission yeast defective in ubiquinone production due to disruption of the gene for p-hydroxybenzoate polyprenyl diphosphate transferase. J. Bacteriol. 2000;182:6933–6939.10.1128/JB.182.24.6933-6939.2000
  • Ashby MN, Kutsunai SY, Ackerman S, Tzagoloff A, Edwards PA. COQ2 is a candidate for the structural gene encoding para-hydroxybenzoate:polyprenyltransferase. J. Biol. Chem. 1992;267:4128–4136.
  • Suzuki K, Ueda M, Yuasa M, Nakagawa T, Kawamukai M, Matsuda H. Evidence that Escherichia coli ubiA product is a functional homolog of yeast COQ2, and the regulation of ubiA gene expression. Biosci. Biotech. Biochem. 1994;58:1814–1819.10.1271/bbb.58.1814
  • Okada K, Ohara K, Yazaki K, et al. The AtPPT1 gene encoding 4-hydroxybenzoate polyprenyl diphosphate transferase in ubiquinone biosynthesis is required for embryo development in Arabidopsis thaliana. Plant Mol. Biol. 2004;55:567–577.
  • Marbois B, Xie LX, Choi S, Hirano K, Hyman K, Clarke CF. para-aminobenzoic acid is a precursor in coenzyme Q6 biosynthesis in Saccharomyces cerevisiae. J. Biol. Chem. 2010;285:27827–27838.10.1074/jbc.M110.151894
  • Pierrel F, Hamelin O, Douki T, et al. Involvement of mitochondrial ferredoxin and para-aminobenzoic acid in yeast coenzyme Q biosynthesis. Chem. Biol. 2010;17:449–459.10.1016/j.chembiol.2010.03.014
  • Cheng W, Li W. Structural insights into ubiquinone biosynthesis in membranes. Science. 2014;343:878–881.10.1126/science.1246774
  • Quinzii C, Naini A, Salviati L, et al. A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am. J. Hum. Genet. 2006;78:345–349.10.1086/500092
  • Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, et al. COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J. Am. Soc. Nephrol. 2007;18:2773–2780.10.1681/ASN.2006080833
  • Poon WW, Barkovich RJ, Hsu AY, et al. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 1999;274:21665–21672.10.1074/jbc.274.31.21665
  • Jonassen T, Clarke CF. Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. J. Biol. Chem. 2000;275:12381–12387.10.1074/jbc.275.17.12381
  • Hsu AY, Poon WW, Shepherd JA, Myles DC, Clarke CF. Complementation of coq3 mutant yeast by mitochondrial targeting of the Escherichia coli UbiG polypeptide: evidence that UbiG catalyzes both O-methylation steps in ubiquinone biosynthesis. Biochemistry. 1996;35:9797–9806.10.1021/bi9602932
  • Miki R, Saiki R, Ozoe Y, Kawamukai M. Comparison of a coq7 deletion mutant with other respiration-defective mutants in fission yeast. FEBS J. 2008;275:5309–5324.10.1111/j.1742-4658.2008.06661.x
  • Hihi AK, Gao Y, Hekimi S. Ubiquinone is necessary for Caenorhabditis elegans development at mitochondrial and non-mitochondrial sites. J. Biol. Chem. 2002;277:2202–2206.10.1074/jbc.M109034200
  • Marbois B, Gin P, Gulmezian M, Clarke CF. The yeast Coq4 polypeptide organizes a mitochondrial protein complex essential for coenzyme Q biosynthesis. Biochim. Biophys. Acta. 2009;1791:69–75.10.1016/j.bbalip.2008.10.006
  • Salviati L, et al. Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency. J. Med. Genet. 2012;49:187–191.10.1136/jmedgenet-2011-100394
  • Barkovich RJ, Shtanko A, Shepherd JA, et al. Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methlytransferase in ubiquinone biosynthesis. J. Biol. Chem. 1997;272:9182–9188.
  • Dai YN, Zhou K, Cao DD, et al. Crystal structures and catalytic mechanism of the C-methyltransferase Coq5 provide insights into a key step of the yeast coenzyme Q synthesis pathway. Acta Crystallogr. D. Biol. Crystallogr. 2014;70:2085–2092.10.1107/S1399004714011559
  • Gin P, Hsu AY, Rothman SC, et al. The Saccharomyces cerevisiae COQ6 gene encodes a mitochondrial flavin-dependent monooxygenase required for coenzyme Q biosynthesis. J. Biol. Chem. 2003;278:25308–25316.10.1074/jbc.M303234200
  • Ozeir M, Mühlenhoff U, Webert H, Lill R, Fontecave M, Pierrel F. Coenzyme Q biosynthesis: Coq6 is required for the C5-Hydroxylation reaction and substrate analogs rescue Coq6 deficiency. Chem. Biol. 2011;18:1134–1142.10.1016/j.chembiol.2011.07.008
  • Heeringa SF, et al. COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J. Clin. Invest. 2011;121:2013–2024.10.1172/JCI45693
  • Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S. Structural and functional conservation of the caenorhabditis elegans timing gene clk-1. Science. 1997;275:980–983.10.1126/science.275.5302.980
  • Nakai D, Shimizu T, Nojiri H, et al. coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q. Aging Cell. 2004;3:273–281.10.1111/ace.2004.3.issue-5
  • Larsen PL, Clarke CF. Extension of life-span in caenorhabditis elegans by a diet lacking coenzyme Q. Science. 2002;295:120–123.10.1126/science.1064653
  • Martín‑Montalvo A, González‑Mariscal I, Padilla S, et al. Respiratory-induced coenzyme Q biosynthesis is regulated by a phosphorylation cycle of Cat5p/Coq7p. Biochem. J. 2011;440:107–114.10.1042/BJ20101422
  • Hsieh EJ, Dinoso JB, Clarke CF. A tRNATRP gene mediates the suppression of cbs2-223 previously attributed to ABC1/COQ8. Biochem. Biophys. Res. Commun. 2004;317:648–653.10.1016/j.bbrc.2004.03.096
  • Saiki R, Ogiyama Y, Kainou T, Nishi T, Matsuda H, Kawamukai M. Pleiotropic phenotypes of fission yeast defective in ubiquinone-10 production. A study from the abc1Sp (coq8Sp) mutant. Biofactors. 2003;18:229–235.10.1002/biof.v18:1/4
  • Tauche A, Krause-Buchholz U, Rodel G. Ubiquinone biosynthesis in Saccharomyces cerevisiae: the molecular organization of O-methylase Coq3p depends on Abc1p/Coq8p. FEMS Yeast Res. 2008;8:1263–1275.10.1111/fyr.2008.8.issue-8
  • Stefely JA, Reidenbach AG, Ulbrich A, et al. Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme q biosynthesis. Mol. Cell. 2015;57:83–94.10.1016/j.molcel.2014.11.002
  • Ashraf S, Gee HY, Woerner S, et al. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J. Clin. Invest. 2013;123:5179–5189.10.1172/JCI69000
  • Lagier-Tourenne C, Tazir M, López LC, et al. ADCK3, an Ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am. J. Hum. Genet. 2008;82:661–672.10.1016/j.ajhg.2007.12.024
  • Johnson A, Gin P, Marbois BN, et al. COQ9, a new gene required for the biosynthesis of coenzyme Q in Saccharomyces cerevisiae. J. Biol. Chem. 2005;280:31397–31404.10.1074/jbc.M503277200
  • Hsieh EJ, Gin P, Gulmezian M, et al. Saccharomyces cerevisiae Coq9 polypeptide is a subunit of the mitochondrial coenzyme Q biosynthetic complex. Arch. Biochem. Biophys. 2007;463:19–26.10.1016/j.abb.2007.02.016
  • He CH, Black DS, Nguyen TP, Wang C, Srinivasan C, Clarke CF. Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid, Biochim. Biophys. Acta. 2015;1851:1227–1239.
  • Lohman DC, Forouhar F, Beebe ET, et al. Mitochondrial COQ9 is a lipid-binding protein that associates with COQ7 to enable coenzyme Q biosynthesis. Proc. Natl. Acad. Sci. U S A. 2014;111:E4697–E4705.10.1073/pnas.1413128111
  • Duncan AJ, Bitner-Glindzicz M, Meunier B, et al. A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset Primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Am. J. Hum. Genet. 2009;84:558–566.10.1016/j.ajhg.2009.03.018
  • Barros MH, Johnson A, Gin P, Marbois BN, Clarke CF, Tzagoloff A. The Saccharomyces cerevisiae COQ10 gene encodes a START domain protein required for function of coenzyme Q in respiration. J. Biol. Chem. 2005;280:42627–42635.10.1074/jbc.M510768200
  • Cui T-Z, Kawamukai M. Coq10, a mitochondrial coenzyme Q binding protein, is required for proper respiration in Schizosaccharomyces pombe. FEBS J. 2009;276:748–759.10.1111/j.1742-4658.2008.06821.x
  • Busso C, Tahara EB, Ogusucu R, et al. Saccharomyces cerevisiae coq10 null mutants are responsive to antimycin A. FEBS J. 2010;277:4530–4538.10.1111/j.1742-4658.2010.07862.x
  • Murai M, Matsunobu K, Kudo S, Ifuku K, Kawamukai M, Miyoshi H. Identification of the binding site of the quinone-head group in mitochondrial Coq10 by photoaffinity labeling. Biochemistry. 2014;53:3995–4003.10.1021/bi500347s
  • Allan CM, Awad AM, Johnson JS, et al. Identification of Coq11, a new coenzyme Q biosynthetic protein in the CoQ-synthome in Saccharomyces cerevisiae. J. Biol. Chem. 2015;290:7517–7534.10.1074/jbc.M114.633131
  • Rea SL, Graham BH, Nakamaru-Ogiso E, Kar A, Falk MJ. Bacteria, yeast, worms, and flies: exploiting simple model organisms to investigate human mitochondrial diseases. Dev. Disabil. Res. Rev. 2010;16:200–218.10.1002/ddrr.v16:2
  • Jacewicz A, Izumi A, Brunner K, Schnell R, Schneider G. Structural insights into the UbiD Protein family from the crystal structure of PA0254 from Pseudomonas aeruginosa. PLoS ONE. 2013;8:e63161.10.1371/journal.pone.0063161
  • Rangarajan ES, Li Y, Iannuzzi P, et al. Crystal structure of a dodecameric FMN-dependent UbiX-like decarboxylase (Pad1) from Escherichia coli O157: H7. Protein Sci. 2004;13:3006–3016.
  • Mukai N, Masaki K, Fujii T, Kawamukai M, Iefuji H. PAD1 and FDC1 are essential for the decarboxylation of phenylacrylic acids in Saccharomyces cerevisiae. J. Biosci. Bioeng. 2010;109:564–569.10.1016/j.jbiosc.2009.11.011
  • Smith N, Roitberg AE, Rivera E, et al. Structural analysis of ligand binding and catalysis in chorismate lyase. Arch. Biochem. Biophys. 2006;445:72–80.10.1016/j.abb.2005.10.026
  • He CH, Xie LX, Allan CM, Tran UC, Clarke CF. Coenzyme Q supplementation or over-expression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants. Biochim. Biophys. Acta. 2014;1841:630–644.10.1016/j.bbalip.2013.12.017
  • Nguyen TP, Casarin A, Desbats MA, et al. Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis. Biochim. Biophys. Acta. 2014;1841:1628–1638.10.1016/j.bbalip.2014.08.007
  • González-Mariscal I, García-Testón E, Padilla S, et al. Regulation of coenzyme Q biosynthesis in yeast: a new complex in the block. IUBMB Life. 2014;66:63–70.10.1002/iub.1243
  • Wang Y, Hekimi S. Molecular genetics of ubiquinone biosynthesis in animals. Critical reviews in biochemistry and molecular biology. 2013;48:69–88.10.3109/10409238.2012.741564
  • Doimo M, Desbats MA, Cerqua C, Cassina M, Trevisson E, Salviati L. Genetics of coenzyme Q10 deficiency. Mol. Syndromol. 2014;5:156–162.
  • Mugoni V, Postel R, Catanzaro V, et al. Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell. 2013;152:504–518.10.1016/j.cell.2013.01.013
  • Hagerman RA, Willis RA. The yeast gene COQ5 is differentially regulated by Mig1p, Rtg3p and Hap2p. Biochim. Biophys. Acta. 2002;1578:51–58.10.1016/S0167-4781(02)00496-7
  • Fischer A, Niklowitz P, Menke T, Döring F. Promotion of growth by Coenzyme Q10 is linked to gene expression in C. elegans. Biochem. Biophys. Res. Commun. 2014;452:920–927.10.1016/j.bbrc.2014.09.016
  • Fernandez-Ayala DJ, Guerra I, Jimenez-Gancedo S, et al. Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies, BMJ Open, 2013;3:e002524.
  • Cluis CP, Burja AM, Martin VJ. Current prospects for the production of coenzyme Q10 in microbes. Trends Biotechnol. 2007;25:514–521.10.1016/j.tibtech.2007.08.008
  • Zahiri HS, Yoon SH, Keasling JD, et al. Coenzyme Q10 production in recombinant Escherichia coli strains engineered with a heterologous decaprenyl diphosphate synthase gene and foreign mevalonate pathway. Metab. Eng. 2006;8:406–416.10.1016/j.ymben.2006.05.002
  • Yoshida H, Kotani Y, Ochiai K, Araki K. Production of ubiquinone-10 using bacteria. J. Gen. Appl. Microbiol. 1998;44:19–26.10.2323/jgam.44.19
  • Ha SJ, Kim SY, Seo JH, et al. Ca2+ increases the specific coenzyme Q10 content in Agrobacterium tumefaciens. Bioprocess. Biosyst. Eng. 2009;32:697–700.
  • Moriyama D, Hosono K, Fujii M, et al. Production of CoQ10 in fission yeast by expression of genes responsible for CoQ10 biosynthesis. Biosci. Biotechnol. Biochem.. 2015;79:1026–1033.
  • Takahashi S, Ogiyama Y, Kusano H, Shimada H, Kawamukai M, Kadowaki K. Metabolic engineering of coenzyme Q by modification of isoprenoid side chain in plant. FEBS Lett. 2006;580:955–959.10.1016/j.febslet.2006.01.023
  • Takahashi S, Ohtani T, Satoh H, Nakamura Y, Kawamukai M, Kadowaki K. Development of coenzyme Q10-enriched rice using sugary and shrunken mutants. Biosci. Biotechnol. Biochem. 2010;74:182–184.10.1271/bbb.90562
  • Mitsui J, Matsukawa T, Ishiura H, et al.. Mutations in COQ2 in familial and sporadic multiple-system atrophy. N. Engl. J. Med. 2013;369:233–244.
  • Mollet J, Delahodde A, Serre V, et al. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am. J. Hum. Genet. 2008;82:623–630.10.1016/j.ajhg.2007.12.022
  • Gerards M, van den Bosch B, Calis C, et al. Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and atrophy. Mitochondrion. 2010;10:510–515.10.1016/j.mito.2010.05.008

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