Overexpression of the Coq8 Kinase in Saccharomyces cerevisiae coq Null Mutants Allows for Accumulation of Diagnostic Intermediates of the Coenzyme Q6 Biosynthetic Pathway

Xie, Letian X.; Ozeir, Mohammad; Tang, J.; Chen, Jia Y.; Jaquinod, Sylvie-Kieffer; Fontecave, Marc; Clarke, Catherine F.; Pierrel, Fabien

doi:10.1074/jbc.m112.360354

Cited by 89 publications

(205 citation statements)

References 41 publications

(85 reference statements)

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“…The di-hydroxyl derivatives of CoQ-0, which are one of the products detected, have a strong potential to form stable complexes with Ca 2+ ions. The importance of the hydroxylated CoQ-0 described in this work is quite intelligible, since some derivatives are recognized as a starting material and/or intermediates in the synthesis of CoQ-members [2,4,39]. Moreover, we have also shown that these hydroxyl derivatives of CoQ-0 have a very strong antioxidative potential comparable to that of Vitamin C. In the future, hydroxylated CoQ-0 compounds should be isolated to further facilitate their chemical analysis and to test their application as antioxidants or divalent cation chelators in biomedical systems.…”

Section: Discussionmentioning

confidence: 99%

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

Gulaboski

Bogeski

Kokoškarova

et al. 2016

Bioelectrochemistry

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Coenzyme Q-0 (CoQ-0) is the only Coenzyme Q lacking an isoprenoid group on the quinoid ring, a feature important for its physico-chemical properties. Here, the redox behavior of CoQ-0 in buffered and non-buffered aqueous media was examined. In buffered aqueous media CoQ-0 redox chemistry can be described by a 2-electron-2-proton redox scheme, characteristic for all benzoquinones. In non-buffered media the number of electrons involved in the electrode reaction of CoQ-0 is still 2; however, the number of protons involved varies between 0 and 2. This results in two additional voltammetric signals, attributed to 2-electrons-1H + and 2-electrons-0H + redox processes, in which mono-and di-anionic compounds of CoQ-0 are formed. In addition, CoQ-0 exhibits a complex chemistry in strong alkaline environment. The reaction of CoQ-0 and OH − anions generates several hydroxyl derivatives as products. Their structures were identified with HPLC/MS. The prevailing radical reaction mechanism was analyzed by electron paramagnetic resonance spectroscopy. The hydroxyl derivatives of CoQ-0 have a strong antioxidative potential and form stable complexes with Ca 2+ ions. In summary, our results allow mechanistic insights into the redox properties of CoQ-0 and its hydroxylated derivatives and provide hints on possible applications.

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Section: Discussionmentioning

confidence: 99%

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

Gulaboski

Bogeski

Kokoškarova

et al. 2016

Bioelectrochemistry

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“…Over-expression of Coq8 restores steady state levels of several of the Coq polypeptides, and enables the synthesis of late-stage Q-intermediates in several of the coq null mutants [17]. To investigate whether over-expression of Coq8 stabilizes high molecular mass Coq polypeptide complexes, mitochondria were prepared from coq null mutant yeast over-expressing Coq8, and digitonin extracts were separated by twodimensional blue native/SDS PAGE.…”

Section: The Coq4 and Coq9 Polypeptides Are Sensitive Indicators Of Tmentioning

confidence: 99%

“…5). In the coq5, coq6 and coq7 null mutants, over-expression of Coq8 enables synthesis of late-stage Q-intermediates: coq5 null mutant accumulates DDMQ 6 , coq6 null accumulates 4-HP (with 4-HB as precursor) and 4-AP (with pABA as precursor), and coq7 null accumulates DMQ 6 [17]. Coq4 steady-state levels decrease dramatically in the coq9 null mutant, but a small amount of Coq4 is detected near 669 kDa.…”

Section: The Coq4 and Coq9 Polypeptides Are Sensitive Indicators Of Tmentioning

confidence: 99%

“…Yeast coq7 null mutants cultured in the presence of exogenous Q 6 were able to synthesize DMQ 6 , and steady-state levels of Coq4 polypeptides were restored, indicating that the presence of Q 6 itself may stabilize the Coq polypeptide complexes [23,34]. Over-expression of Coq8 has no effect on either the coq1 or coq2 null mutants [17], which lack the ability to synthesize polyisoprenylated ring intermediates. This indicates that a polyisoprenylated component is essential for complex formation.…”

Section: Introductionmentioning

confidence: 98%

“…Coq4, Coq8, and Coq9 polypeptides are essential for Q biosynthesis but their functional roles are not yet completely understood. In the Qbiosynthetic pathway proceeding from pABA, Coq9 is required for the replacement of the ring amino substituent with a hydroxyl group, although it remains uncertain exactly how this step is carried out [17].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Coenzyme Q supplementation or Over-Expression of the Yeast Coq8 Putative Kinase Stabilizes Multi-Subunit Coq Polypeptide Complexes in Yeast Coq Null Mutants

Xie

Allan

et al. 2013

Free Radical Biology and Medicine

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Regulation of coenzyme Q biosynthesis in yeast: A new complex in the block

et al. 2014

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Coenzyme Q (CoQ) is an isoprenylated benzoquinone found in mitochondria, which functions mainly as an electron carrier from complex I or II to complex III in the inner membrane. CoQ is also an antioxidant that specifically prevents the oxidation of lipoproteins and the plasma membrane. Most of the information about the synthesis of CoQ comes from studies performed in Saccharomyces cerevisiae. CoQ biosynthesis is a highly regulated process of sequential modifications of the benzene ring. There are three pieces of evidence supporting the involvement of a multienzymatic complex in yeast CoQ 6 biosynthesis: (a) the accumulation of a unique early precursor in all null mutants of the COQ genes series, 4-hydroxy-3-hexaprenyl benzoate (HHB), (b) the lack of expression of several Coq proteins in COQ null mutants, and (c) the restoration of CoQ biosynthesis complex after COQ8 overexpression. The model we propose based on the formation of a multiprotein complex should facilitate a better understanding of CoQ biosynthesis. According to this model, the complex assembly requires the synthesis of a precursor such as HHB by Coq2p that must be recognized by the regulatory protein Coq4p to act as the core component of the complex. The phosphorylation of Coq3p and Coq5p by the kinase Coq8p facilitates the formation of an initial precomplex of 700 kDa that contains all Coq proteins with the exception of Coq7p. The precomplex is required for the synthesis of 5-demethoxy-Q 6 , the substrate of Coq7p. When cells require de novo CoQ 6 synthesis, Coq7p is dephosphorylated by Ptc7p, a mitochondrial phosphatase that activates the synthesis of CoQ 6. This event allows for the full assembly of a complex of 1,300 kDa that is responsible for the final product of the pathway, CoQ 6 .

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Overexpression of the Coq8 Kinase in Saccharomyces cerevisiae coq Null Mutants Allows for Accumulation of Diagnostic Intermediates of the Coenzyme Q6 Biosynthetic Pathway

Cited by 89 publications

References 41 publications

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

Coenzyme Q supplementation or Over-Expression of the Yeast Coq8 Putative Kinase Stabilizes Multi-Subunit Coq Polypeptide Complexes in Yeast Coq Null Mutants

Regulation of coenzyme Q biosynthesis in yeast: A new complex in the block

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