Coenzyme Q (referred to simply as Q) is a lipophilic component of the electron transport chain in mitochondria. The biosynthesis of Q is known to include several steps, including two O-methyltransferase reactions catalyzed by COQ-3. The
coq-3 gene is well-conserved among various organisms, from Homo sapiens to E. col, where the gene is termed ubiG. Expression of C. elegans COQ-3 restores respiratory growth and Q biosynthesis in an E. coli ubiG mutant, and in a S. cerevisiae
coq-3 mutant. In C. elegans,
coq-3 mutants demonstrate decreased fertility, activity, survival and behavior. One mutant,
coq-3(
qm188), possesses a deletion of the third and fourth exons. Sequencing of the
coq-3(
qm188) mRNA transcript shows a spliced product containing exons 1, 2 and 5 in a complete reading frame. Another mutant,
coq-3(
ok506), is missing exon 3 only; however, the spliced mRNA is frameshifted and is predicted to generate an early stop codon. Interestingly,
coq-3(
qm188) mutants are sterile on a Q-replete bacterial diet of OP50, whereas
coq-3(
ok506) mutants generate approximately 100 larvae that arrest at the L1 stage. Both mutant strains are sterile and when fed the Q-deficient bacteria strain GD-1. Neither the
coq-3(
qm188), nor the
coq-3(
ok506) mutant is rescued, however, when grown on media containing NovaSol Q10, a lipid-soluble coenzyme Q10 delivery system. RT-PCR conducted on these strains shows mRNA product of the predicted sizes for both strains. Sequencing of these transcripts reveals no cryptic splice sites. The
coq-3 gene is situated in a three-gene operon. Transcripts of the flanking genes in the operon from the
coq-3(
qm188) mutant allele are present, as evaluated via RT-PCR. Currently we are optimizing small-scale quinone analysis in lipid extracts of 50 adults worms via HPLC-MS/MS.