Resveratrol is converted to the ring portion of coenzyme Q10 and raises intracellular coenzyme Q10 levels in HepG2 cell.

Coenzyme Q10 is an essential lipid in the mitochondrial electron transport system and an important antioxidant. It declines with age and in various diseases, there is a need for a method to compensate for the decrease in coenzyme Q10. Resveratrol, a well-known anti-aging compound, has been shown to undergo metabolism to coenzyme Q10's benzene ring moiety in cells. However, administration of resveratrol did not alter or only slightly increased total intracellular coenzyme Q10 levels in many cell types. Synthesis of coenzyme Q10 requires not only the benzene ring moiety but also the side chain moiety. Biosynthesis of the side chain portion of coenzyme Q10 is mediated by the mevalonic acid pathway. Here, we explore the impact of resveratrol on coenzyme Q10 levels in HepG2 cells, which possess a robust mevalonic acid pathway. As a results, intracellular coenzyme Q10 levels were increased by resveratrol administration. Analysis using 13C6-resveratrol revealed that the benzene ring portion of resveratrol was converted to coenzyme Q10. Inhibition of the mevalonic acid pathway prevented the increase in coenzyme Q10 levels induced by resveratrol administration. These results indicate that resveratrol may be beneficial as a coenzyme Q10-enhancing reagent in cells with a well-developed mevalonic acid pathway.

Transferrin, insulin, and progesterone modulate intracellular concentrations of coenzyme Q and cholesterol, products of the mevalonate pathway, in undifferentiated PC12 cells.

Coenzyme Q (CoQ) is important not only as an essential lipid for the mitochondrial electron transport system, but also as an antioxidant. CoQ levels decrease during aging and in various diseases. Orally administered CoQ is not readily taken up in the brain, so it is necessary to develop a method to increase the amount of CoQ in neurons. CoQ is synthesized via mevalonate pathway, like cholesterol. Transferrin, insulin, and progesterone are factors used in the culture of neurons. In this study, we determined the effect of these reagents on cellular CoQ and cholesterol levels. The administration of transferrin, insulin, and progesterone increased cellular CoQ levels in undifferentiated PC12 cells. When serum was removed and only insulin was administered, intracellular CoQ levels increased. This increase was even more pronounced with concurrent administration of transferrin, insulin, and progesterone. Cholesterol level decreased by the administration of transferrin, insulin, and progesterone. Progesterone treatment lowered intracellular cholesterol levels in a concentration-dependent manner. Our findings suggest that transferrin, insulin, and progesterone may be useful in regulating CoQ levels and cholesterol levels, which are products of the mevalonate pathway.