COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10

Abstract

Coenzyme Q (Q _n ) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1-coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q₆ The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q₆ at an impaired rate. Thus, Coq10 is required for the function of Q₆ in respiration and as an antioxidant and is believed to chaperone Q₆ from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q₆ biosynthesis. Because "fused" proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q₆ biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q₆ biosynthesis and that its absence increases mitochondrial Q₆ content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q₆ content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q₆ biosynthesis, trafficking, and function in mitochondrial metabolism.

Keywords: CoQ synthome; Coq10; Coq11; Saccharomyces cerevisiae; coenzyme Q; lipid; mitochondrial metabolism; ubiquinone; yeast.