CLD1 Reverses the Ubiquinone Insufficiency of Mutant cat5/coq7 in a Saccharomyces cerevisiae Model System.

摘要: Ubiquinone (Qn) functions as a mobile electron carrier in mitochondria. In humans, Q biosynthetic pathway mutations lead to Q10 deficiency, life threatening disorder. We have used Saccharomyces cerevisiae model of Q6 deficiency screen for new modulators ubiquinone biosynthesis. generated several hypomorphic alleles coq7/cat5 (clk-1 Caenorhabditis elegans) encoding the penultimate enzyme biosynthesis which converts 5-demethoxy (DMQ6) 5-demethyl Q6, and screened genes that, when overexpressed, suppressed their inability grow on non-fermentable ethanol—implying recovery lost mitochondrial function. Through this approach we identified Cardiolipin-specific Deacylase 1 (CLD1), gene phospholipase A2 required cardiolipin acyl remodeling. Interestingly, not all coq7 mutants were by Cld1p overexpression, molecular modeling mutant Coq7p proteins that showed they contained disruptions hydrophobic α-helix is predicted mediate membrane-binding. CLD1 overexpression suppressible restored ratio DMQ6 toward wild type levels, suggesting Identification spontaneous loss-of-function mutation illustrated activity was suppression. This observation further supported HPLC-ESI-MS/MS profiling monolysocardiolipin, product Cld1p. summary, our results present novel example lipid remodeling reversing insufficiency facilitating enzymatic