Coq9 regulates the deamination of Q6‐intermediates in yeast Q biosynthesis and human Coq9 homolog rescues yeast coq9 mutant by increasing the incorporation of 4‐hydroxybenzoic acid

Coq9 is a subunit in a mitochondrial complex, termed the CoQ‐synthome, required for the biosynthesis of coenzyme Q. Deletion of COQ9 results in the dissociation of the CoQ‐synthome, but over‐expression of Coq8 stabilizes it and leads to the accumulation of imino‐demethoxy‐Q 6 (IDMQ 6 ) and 3‐hexaprenyl‐4‐aminophenol (4‐ AP) when para‐aminobenzoic acid (pABA) is provided. To investigate if Coq9 is responsible for deamination steps, we utilized the yeast coq5‐5 point mutant. When high amounts of 13 C 6 ‐ pABA are provided, coq5‐5 accumulates both 13 C 6 ‐imino‐demethyl‐demethoxy Q 6 ( 13 C 6 ‐ IDDMQ 6 ) and demethyl‐demethoxy‐Q 6 ( 13 C 6 ‐ DDMQ 6 ). The deletion of COQ9 in coq5‐5 along with Coq8 over expression and 13 C 6 ‐pABA labeling leads to accumulation of 13 C 6 ‐4‐AP and 13 C6‐IDDMQ6 but not 13 C 6 ‐DDMQ 6 . We describe a coq9 mutant and show that at the non‐permissive temperature, polypeptide levels of Coq9‐ts19 were increased, while Coq4, Coq7 and Coq5 were decreased. The coq9‐ts19 mutant had decreased Q 6 and increased levels of imino‐/amino‐Q‐intermediates. These findings indicate that Coq9 is required for the deamination step. Expression of human COQ9 rescues the growth of coq9‐ts19 mutant yeast on respiratory carbon source and increases Q6, by enhancing Q biosynthesis from 4‐hydroxybenzoic acid (4HB). This finding provides a powerful approach to study the function of human Coq9 using yeast as a model This research was supported by NSF MCB‐1330803