Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene.

Clarke, Catherine F.; Williams, Wendy; Teruya, J H

doi:10.1016/s0021-9258(18)55349-7

Cited by 77 publications

(17 citation statements)

References 49 publications

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“…Characterization of COQ7 mRNA-Analysis of the induction of the message for the COQ7 gene shows that it is regulated in a manner similar to that of the COQ3 gene (17). Growth of the wild-type strain D273-10B in YPG induces the production of both genes, as would be expected for genes influencing the function of the respiratory chain (Fig.…”

Section: Resultsmentioning

confidence: 84%

“…In Vivo Labeling of Q 6 and Q 6 Intermediates and Lipid Extraction-[carboxyl- 14 C]p-hydroxybenzoic acid (50 Ci/mol) was from RPI Corp. (Mount Prospect, IL) and [U- 14 C]p-hydroxybenzoic acid (365 Ci/mol) was synthesized from L-[U- 14 C]tyrosine (469 Ci/mol, DuPont NEN) by alkali heat fusion as described by Clarke et al (17). [U- 14 C]p-Hydroxybenzoic acid was added to the SD complete medium yeast cultures before inoculation (0.65 Ci/liter).…”

Section: Methodsmentioning

confidence: 99%

“…Probes were labeled with [␣- 32 P]dCTP (3000 Ci/mmol, ICN Biomedicals, Inc.) with an oligolabeling kit (Pharmacia) and unincorporated nucleotides were removed with NucTrap® push columns (Stratagene). Northern blots were hybridized with 32 P-labeled DNA probes corresponding to either a segment of the yeast COQ3 gene, a 0.7-kb BglII fragment isolated from pRS12A-2.5SB, (17), or a segment of DNA containing the COQ7 gene (1.9-kb HindIII to XhoI restriction fragment from pNMQ7). This blot was subsequently re-probed with a clathrin heavy chain CHC1 gene present in the plasmid pCHC101 (37) after expiration of 12 32 P half-lives.…”

Section: Methodsmentioning

confidence: 99%

“…In S. cerevisiae synthesis of compound 1 is carried out by enzymes encoded by the COQ1 and COQ2 genes (15,16). The COQ3 gene encodes an O-methyltransferase thought to catalyze the synthesis of compound 5 (17). Evidence for the branched pathways between prokaryotes and eukaryotes derives from the isolation of compound 2 (Fig.…”

Section: Ubiquinone (Coenzyme Q) Is a Lipid That Transports Electrons In The Respiratory Chains Of Both Prokaryotes And Eukaryotes Mutantmentioning

confidence: 99%

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The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

Marbois

Clarke

1996

Journal of Biological Chemistry

177

159

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Ubiquinone (coenzyme Q) is a lipid that transports electrons in the respiratory chains of both prokaryotes and eukaryotes. Mutants of Saccharomyces cerevisiae deficient in ubiquinone biosynthesis fail to grow on nonfermentable carbon sources and have been classified into eight complementation groups (coq1 coq8; Tzagoloff, A., and Dieckmann, C. L.(1990) Microbiol. Rev. 54, 211-225). In this study we show that although yeast coq7 mutants lack detectable ubiquinone, the coq7 1 mutant does synthesize demethoxyubiquinone (2-hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinone), a ubiquinone biosynthetic intermediate. The corresponding wild-type COQ7 gene was isolated, sequenced, and found to restore growth on nonfermentable carbon sources and the synthesis of ubiquinone. The sequence predicts a polypeptide of 272 amino acids which is 40% identical to a previously reported Caenorhabditis elegans open reading frame. Deletion of the chromosomal COQ7 gene generates respiration defective yeast mutants deficient in ubiquinone. Analysis of several coq7 deletion strains indicates that, unlike the coq7 1 mutant, demethoxyubiquinone is not produced. Both coq7 1 and coq7 deletion mutants, like other coq mutants, accumulate an early intermediate in the ubiquinone biosynthetic pathway, 3-hexaprenyl-4-hydroxybenzoate. The data suggest that the yeast COQ7 gene may encode a protein involved in one or more monoxygenase or hydroxylase steps of ubiquinone biosynthesis.

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Section: Resultsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ubiquinone (Coenzyme Q) Is a Lipid That Transports Electrons In The Respiratory Chains Of Both Prokaryotes And Eukaryotes Mutantmentioning

confidence: 99%

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The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

Marbois

Clarke

1996

Journal of Biological Chemistry

177

159

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“…In humans, mutations have so far been reported in all the genes required for CoQ 10 biosynthesis, except COQ3 . COQ3 is an O-methyltransferase and it is the only COQ protein that is required for more than one step in the CoQ biosynthetic pathway [46]. Thus, one possible explanation for the lack of reports of COQ3 patients is that, because it is required for two enzymatic steps, pathogenic mutations in COQ3 are more detrimental to CoQ production and thus are more likely to be lethal.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of coenzyme Q₁₀treatment in alleviating the symptoms of primary coenzyme Q₁₀deficiency: a systematic review

Wang

Hekimi

2022

Preprint

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Coenzyme Q10 (CoQ10) is necessary for mitochondrial electron transport. Mutations in CoQ10 biosynthetic genes cause primary CoQ10 deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ10 supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ10 treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ10 treatment (27.0%). In five cases, the patient’s condition was reported to deteriorate after halting of CoQ10 treatment. 12 cases reported improvement in the severity of ataxia, and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for four patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ10 supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings thus suggest a need for caution when seeking to justify the widespread use of CoQ10 for the treatment of any disease or as dietary supplement.HighlightsOnly 27% of primary CoQ10 deficiency patients benefited from CoQ10 supplementation.Studies of the effects of supplementation necessarily lacked controls and blinding.All reported positive responses to treatment only partially improved few symptoms.CoQ10 supplementation for the treatment of any disease should be questioned.Firm evidence of benefits requires randomize, controlled trials of CoQ10 therapy.Graphic Abstract

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Chemical proteomic study of isoprenoid chain interactome with a synthetic photoaffinity probe

Tian

Tang

et al. 2008

Proteomics

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A chemical proteomic approach was developed for profiling the noncovalent interactome of isoprenoid chain in the yeast proteome. A chemical probe that harbors a biotin moiety and a photoreactive benzophenone group linked to the terminal of geranyl group was synthesized. Photoaffinity labeling was performed by incubating the Saccharomyces cerevisiae proteome and the probe under 365 nm UV light. Thirty proteins were identified by immobilized NeutraAvidin enrichment, on-bead digestion, online 2-D nano-LC/MS/MS identification and semi-quantitative proteomic analysis. As noted by Gene Ontology annotation, the identified proteins demonstrate a wide range of catalytic activity in several biological processes, especially in metabolism and biosynthesis. Further data analysis shows that hydrophobic binding of the synthetic probe is potentially the major interaction force leading to covalent labeling. These results argue that intracellular allosteric interactions conferred by the isoprenoid chain of the corresponding chemical structures may be widespread at an interactomic level.

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Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene.

Cited by 77 publications

References 49 publications

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

The efficacy of coenzyme Q₁₀treatment in alleviating the symptoms of primary coenzyme Q₁₀deficiency: a systematic review

Chemical proteomic study of isoprenoid chain interactome with a synthetic photoaffinity probe

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Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene.

Cited by 77 publications

References 49 publications

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis

The efficacy of coenzyme Q10treatment in alleviating the symptoms of primary coenzyme Q10deficiency: a systematic review

Chemical proteomic study of isoprenoid chain interactome with a synthetic photoaffinity probe

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The efficacy of coenzyme Q₁₀treatment in alleviating the symptoms of primary coenzyme Q₁₀deficiency: a systematic review