Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q2. Rescue of respiration by Q2 is a characteristic of mutants blocked in coenzyme Q6 synthesis. Unlike Q6 deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations of Q6. The physiological significance of earlier observations that purified Coq10p contains bound Q6 was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q2. This suggests that in vivo binding of Q6 by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains over-producing Coq10p.

Research highlights
► COQ10 deletion elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q2, a synthetic diffusible ubiquinone.
► The significance that purified Coq10p contains bound Q6 was examined by testing over-expression of Coq10p on respiration.
► Inhibition of CoQ function due to Coq10p excess strength our hypothesis of Coq10p function in CoQ delivery.
► Respiratory deficiency caused by more Coq10p was specific and restored by Q2 in mitochondria or by Coq8p in cells.
► Coq8p over-production on other coq mutants revealed a surprisingly higher stability of other Coq proteins.