The effect of SIRT1 knockdown on the gene expression of CoQ10 biosynthetic enzymes

Coenzyme Q10 is a lipid-soluble antioxidant essential for the mitochondrial electron transport chain. Its concentration in the body decreases with age. The biosynthesis of coenzyme Q10 involves enzymes coq1 (PDSS1, PDSS2) through coq9, though the regulatory mechanisms of their gene expression and enzyme activities are unknown. SIRT1, an anti-aging gene, regulates various transcription factors. This study investigates the impact of SIRT1 knockdown on the gene expression of coenzyme Q10 biosynthetic enzymes and coenzyme Q10 levels in MDA-MB-231 and HepG2 cells. SIRT1 knockdown significantly increased <i>coq4</i> gene expression in MDA-MB-231 cells, while <i>coq6</i> and <i>coq7</i> expression decreased. In HepG2 cells, <i>coq4</i> expression also increased, but <i>coq6</i> and <i>coq7</i> expression remained unchanged. Coenzyme Q10 levels increased in both cell lines. Further experiments with PGC-1α and NRF1 knockdown, downstream factors of SIRT1, in MDA-MB-231 cells showed no change in <i>coq4</i> expression, while <i>coq6</i> and <i>coq7</i> expression decreased, and coenzyme Q10 levels remained unchanged. These findings suggest that the increase in coenzyme Q10 levels following SIRT1 knockdown may be attributed to <i>coq4</i>, indicating a pathway distinct from PGC-1α and NRF1.