Coq3, a gene encoding 3,4-dihydroxy-5-polyprenylbenzoate methyltransferase [3,6], is essential for coenzyme Q (Q) biosynthesis, a redox-active lipid crucial for aerobic respiration in eukaryotes [1]. Q biosynthesis involves at least eight mitochondrial polypeptides in Saccharomyces cerevisiae, with Coq3 being one of them. Coq3 is part of a Q-biosynthetic polypeptide complex in yeast mitochondria along with Coq4 [1].

In yeast, Coq3 is involved in two O-methylation steps in Q biosynthesis, methylating an early Q intermediate and the final intermediate [4,5,6,7]. It has been found that Coq3-related O-methyltransferase activity is associated with a high-molecular-mass complex in yeast mitochondria [1]. In addition, human and yeast Coq3 show a strong preference for liposomes enriched with cardiolipin, a signature lipid of the mitochondrial membrane, indicating it's a membrane-binding protein [2].

In summary, Coq3 is vital for coenzyme Q biosynthesis, functioning through O-methylation steps and being associated with a multi-subunit complex in mitochondria. Although no KO/CKO mouse model-related findings are presented in the references, the studies on yeast and other organisms provide insights into its fundamental role in aerobic respiration-related processes [1,2,3,4,5,6,7].

References:

1. Marbois, Beth, Gin, Peter, Faull, Kym F, Shepherd, Jennifer N, Clarke, Catherine F. 2005. Coq3 and Coq4 define a polypeptide complex in yeast mitochondria for the biosynthesis of coenzyme Q. In The Journal of biological chemistry, 280, 20231-8. doi:. https://pubmed.ncbi.nlm.nih.gov/15792955/

2. Zhu, Yuwei, Wu, Bo, Zhang, Xu, Wang, Junfeng, Teng, Maikun. 2015. Structural and biochemical studies reveal UbiG/Coq3 as a class of novel membrane-binding proteins. In The Biochemical journal, 470, 105-14. doi:10.1042/BJ20150329. https://pubmed.ncbi.nlm.nih.gov/26251450/

3. Marbois, B N, Xia, Y R, Lusis, A J, Clarke, C F. . Ubiquinone biosynthesis in eukaryotic cells: tissue distribution of mRNA encoding 3,4-dihydroxy-5-polyprenylbenzoate methyltransferase in the rat and mapping of the COQ3 gene to mouse chromosome 4. In Archives of biochemistry and biophysics, 313, 83-8. doi:. https://pubmed.ncbi.nlm.nih.gov/8053692/

4. Jonassen, T, Clarke, C F. . Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. In The Journal of biological chemistry, 275, 12381-7. doi:. https://pubmed.ncbi.nlm.nih.gov/10777520/

5. Hsu, A Y, Poon, W W, Shepherd, J A, Myles, D C, Clarke, C F. . Complementation of coq3 mutant yeast by mitochondrial targeting of the Escherichia coli UbiG polypeptide: evidence that UbiG catalyzes both O-methylation steps in ubiquinone biosynthesis. In Biochemistry, 35, 9797-806. doi:. https://pubmed.ncbi.nlm.nih.gov/8703953/

6. Clarke, C F, Williams, W, Teruya, J H. . Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene. In The Journal of biological chemistry, 266, 16636-44. doi:. https://pubmed.ncbi.nlm.nih.gov/1885593/

7. Poon, W W, Barkovich, R J, Hsu, A Y, Myles, D C, Clarke, C F. . Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. In The Journal of biological chemistry, 274, 21665-72. doi:. https://pubmed.ncbi.nlm.nih.gov/10419476/