P-89 - A potential novel pathway to regulate cellular concentrations of the redox-active lipid coenzyme Q.

Coenzyme Q (CoQ) is an essential redox-active lipid, and its deficiency is implicated in numerous diseases. However, it is largely unknown what regulates CoQ content. To investigate cellular CoQ regulation, we performed a genome-wide screen (~5,000 S. cerevisiae single gene mutants) to isolate genes critical for CoQ homeostasis, and measured CoQ content in each mutant using HPLC-EC detection. Some 30 knockout mutants were identified with significantly higher CoQ content compared to WT including the cho2 mutant. CHO2 encodes a phosphatidylethanolamine (PE) methyltransferase that catalyzes the conversion of PE to phosphatidylcholine (PC). Homologs of CHO2 are found in mammals (PEMT) indicating there may be role for this gene in CoQ regulation in other species. The cho2 mutant contained concentrations of CoQ five times greater than WT, and a significantly increased rate of CoQ synthesis. To investigate if Pemt–/– mice also display elevated CoQ content akin to yeast cho2 mutants, we analyzed the CoQ content in liver and adipose tissue from Pemt+/+ and Pemt–/– mice. In these tissues, CoQ content was approximately double in Pemt–/– compared to Pemt+/+. Taken together, our data suggests a novel role for phosphatidylethanolamine methyltransferases in CoQ content regulation. [ABSTRACT FROM AUTHOR]