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

• Published in: Frontiers in physiology 2017-07, Vol.8, p.463-463
• Main Authors: He, Cuiwen H, Black, Dylan S, Allan, Christopher M, Meunier, Brigitte, Rahman, Shamima, Clarke, Catherine F
• Format: Article
• Language: English
• Subjects: coenzyme Q; human homolog; immunoprecipitation; Life Sciences; mitochondrial metabolism; Physiology; Saccharomyces cerevisiae; temperature-sensitive mutant
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2017.00463

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 gene cause neonatal-onset primary Q deficiency. In this study, we determined whether expression of human could complement yeast point or null mutants. We found that expression of human rescues the growth of the temperature-sensitive yeast mutant, , on a non-fermentable carbon source and increases the content of Q , 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 mutant expressing human . We show that the expression of human 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 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.