Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis

Xie, Letian X.; Williams, Kevin J.; He, Cuiwen; Weng, Emily; Khong, San; Rose, Tristan E.; Kwon, Ohyun; Bensinger, Steven J.; Marbois, Beth N.; Clarke, Catherine F.

doi:10.1194/jlr.m057919

Cited by 40 publications

(64 citation statements)

References 53 publications

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“…In the event that Coq5 activity is slow (or defective) then Coq9 is able to process IDDMQ 6 to DDMQ 6 . There are likely to be profound differences between the yeast and human enzymes at these steps, because human cells are unable to convert pABA to Q [17]…”

Section: Discussionmentioning

confidence: 99%

“…This finding suggests that Coq9 is required for Coq7 function, but is also required for deamination of Q-intermediates when pABA is used as a ring precursor. While pABA is utilized to generate Q 6 in yeast, it is not a ring precursor for Q biosynthesis in human, mouse, Arabidopsis thaliana or E. coli [17, 18]. Therefore, the important role that Coq9 plays in the deamination of Q-intermediates might be unique to yeast Coq9.…”

Section: Introductionmentioning

confidence: 99%

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Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid

Black

Nguyen

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Coq9 is a polypeptide subunit in a mitochondrial multi-subunit complex, termed the CoQ-synthome, required for biosynthesis of coenzyme Q (ubiquinone or Q). Deletion of COQ9 results in dissociation of the CoQ-synthome, but over-expression of Coq8 putative kinase stabilizes the CoQ-synthome in the coq9 null mutant and leads to the accumulation of two nitrogen containing Q-intermediates, imino-demethoxy-Q6 (IDMQ6) and 3-hexaprenyl-4-aminophenol (4-AP) when para-aminobenzoic acid (pABA) is provided as a ring precursor. To investigate whether Coq9 is responsible for deamination steps in Q biosynthesis, we utilized the yeast coq5-5 point mutant. The yeast coq5-5 point mutant is defective in the C-methyltransferase step of Q biosynthesis, but retains normal steady-state levels of the Coq5 polypeptide. Here we show that when high amounts of 13C6-pABA are provided, the coq5-5 mutant accumulates both 13C6-imino-demethyl-demethoxy-Q6 (13C6-IDDMQ6) and demethyl-demethoxy-Q6 (13C6-DDMQ6). Deletion of COQ9 in the yeast coq5-5 mutant along with Coq8 over-expression and 13C6-pABA labeling leads to the absence of 13C6-DDMQ6, and the nitrogen-containing intermediates 13C6-4-AP and 13C6-IDDMQ6 persist. We describe a coq9 temperature sensitive mutant and show that at the non-permissive temperature, steady state polypeptide levels of Coq9-ts19 increased, while Coq4, Coq5, Coq6, and Coq7 decreased. The coq9-ts19 mutant had decreased Q6 content and increased levels of nitrogen-containing intermediates. These findings identify Coq9 as a multi-functional protein that is required for the function of Coq6 and Coq7 hydroxylases, for removal of the nitrogen substituent from pABA-derived Q-intermediates, and is an essential component of the CoQ synthome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid

Black

Nguyen

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Recently, it was shown that Arabidopsis does not incorporate pABA into Q, however, it was not established whether pABA is prenylated or not in this organism (15). In E. coli, pABA yields several octaprenyl C4-aminated compounds but no Q 8 (39), implying that the C5-hydroxylase UbiI is not capable of catalyzing the C4-deamination. The potential C4-deamination capacity of a given Coq6 homolog is likely linked to the positioning of carbon C4 of HHAB with regard to the FAD as discussed in the case of L382E and M469X mutants.…”

Section: Proposed Mechanism Of the Dioxygen-mediated Deamination-ourmentioning

confidence: 99%

“…Lacking Coq9 -Several reports document that pABA is not a precursor of Q 10 in different human cell lines (37)(38)(39). Because huCoq6 expressed in S. cerevisiae ⌬coq6 cells partially complements the C5-hydroxylation defect (36), we tested the effect of the addition of pABA to the growth medium.…”

Section: Human Coq6 Supports C4-deamination In Yeast Cellsmentioning

confidence: 99%

Coq6 Is Responsible for the C4-deamination Reaction in Coenzyme Q Biosynthesis in Saccharomyces cerevisiae

Ozeir

Pélosi

Ismail

et al. 2015

Journal of Biological Chemistry

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Background: A deamination reaction is necessary for yeast to synthesize coenzyme Q from para-aminobenzoic acid. Results: The deamination requires dioxygen and an active Coq6 enzyme. Conclusion: The flavin monooxygenase Coq6 is responsible for the substitution of the amino group with a hydroxyl group. Significance: Coq6 hydroxylates two positions of its amino substrate and partly determines whether an organism can synthesize coenzyme Q from para-aminobenzoic acid.

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“…Interestingly, human cells cannot synthesize Q from pABA (Xie et al, 2015). Thus, human COQ9 may lack the ability to aid in the deamination step(s) that are normally required in yeast Q biosynthesis from pABA.…”

Section: Introductionmentioning

confidence: 99%

Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome

Black

Allan

et al. 2017

Front. Physiol.

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Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB). To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model.

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Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis

Cited by 40 publications

References 53 publications

Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid

Yeast Coq9 controls deamination of coenzyme Q intermediates that derive from para-aminobenzoic acid

Coq6 Is Responsible for the C4-deamination Reaction in Coenzyme Q Biosynthesis in Saccharomyces cerevisiae

Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome

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