Baker, Z. N.; Guerra, R. M.; Rogers, S. W.; Pagliarini, D. J.

Coenzyme Q (CoQ, ubiquinone) is a redox-active isoprene lipid that supports fundamental enzymatic and antioxidant roles in mitochondria and beyond. Despite CoQ\'s importance in organismal health and disease, the mechanisms that regulate its biosynthetic pathway remain elusive. Motivated by this, we mined S. cerevisiae multiomics datasets for genes whose disruptions alter CoQ levels and discovered the gene FMP30 as an unexpected negative regulator of CoQ biosynthesis. Loss of FMP30 results in elevated complex Q protein abundance, increased number and intensity of CoQ domains, and ultimately enhanced CoQ biosynthetic flux. We demonstrate that Fmp30, a member of the metallo-{beta}-lactamase super family, displays phospholipase type D activity toward phosphatidylinositol and phosphoinositides, and that its deletion causes marked elevation of these lipid species in purified mitochondria. Collectively, our work nominates Fmp30 as a novel regulator linking mitochondrial phospholipid metabolism to CoQ biosynthesis.