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Biochim Biophys Acta. 2015 Sep;1851(9):1227-39. doi: 10.1016/j.bbalip.2015.05.003. Epub 2015 May 23.

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

Author information

1
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA, USA 90095-1569.
2
Department of Chemistry and Biochemistry, California State University, Fullerton, Fullerton, CA, USA 92834.
3
Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA, USA 90095-1569. Electronic address: cathy@chem.ucla.edu.

Abstract

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 13C6-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.

KEYWORDS:

Coenzyme Q; Mass spectrometry (MS); Mitochondrial metabolism; Q biosynthetic intermediates; Saccharomyces cerevisiae; Temperature-sensitive mutant

PMID:
26008578
PMCID:
PMC4516658
DOI:
10.1016/j.bbalip.2015.05.003
[Indexed for MEDLINE]
Free PMC Article

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