The degree of severity of cardiomyopathy is inversely correlated with tissue levels of coenzyme Q (Q), suggesting that Q synthesis may impact the progression of the disease. It has been suggested that Q functions as an endogenously synthesized anti-oxidant, in addition to regenerating the potent anti-oxidants, vitamins E and C. However, very little is known about the mechanisms that regulate Q synthesis. Using the simple eukaryote Saccharomyces cerevisiae as a model, experiments have been designed to investigate the regulation of Q synthesis at the genetic level. To investigate the regulation of COQ5 gene expression by energy source, mRNA content was evaluated in yeast cells treated with dextrose, glycerol or oleic acid. After 1.5 h, more COQ5 mRNA is produced by oleic acid treated cells than by glycerol treated. Experiments performed using COQ5 promoter deletion/reporter constructs demonstrate a specific response to oleic acid. Additional promoter deletion analysis demonstrates that a non-fermentable carbon source element is also present, responding to both glycerol and oleic acid. The specific oleic acid response appears to be regulated by the Rtg family of transcription factors. This family of proteins is required for oleic acid-induced expression of genes of beta-oxidation and peroxisomal proliferation, and plays an important role in co-ordinating mitochondrial/peroxisomal/nuclear communication in response to oleic acid, as well as defects in cellular respiration.