Phosphatidylglycerophosphate synthase 1 (PGS1)

Phosphatidylglycerophosphate synthase 1 (PGS1) is a mitochondrial inner membrane enzyme that catalyzes the committed step in phosphatidylglycerol and cardiolipin synthesis, transferring a phosphatidyl group from CDP-diacylglycerol to glycerol-3-phosphate to form phosphatidylglycerophosphate (PGP)[1][3]. This pathway is essential for the generation of cardiolipin, a critical component of the mitochondrial inner membrane required for proper function of the electron transport chain and for mitochondrial biogenesis and integrity[4][6]. Reduced or absent PGS1 activity leads to a profound loss of mitochondrial function, including inability to translate several key subunits of the electron transport chain, resulting in cellular energy deficiency and potentially cell death[4]. While essential for mitochondrial metabolism and implicated in metabolic and mitochondrial disorders, PGS1 itself is not currently a direct therapeutic drug target; however, its bacterial homologs are studied for antimicrobial drug development due to their role in antibiotic resistance, such as daptomycin resistance in Staphylococcus aureus[5].

Other names

CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrialPGP synthase 1DKFZP762M186Phosphatidylglycerophosphate synthase 1CDP-diacylglycerol--glycerol-3-phosphate 1-phosphatidyltransferase

Inhibition of PGS1 decreases cardiolipin and mitochondrial phospholipid content, impairing mitochondrial protein translation and function. Its activity can also be modulated by drug-induced changes in upstream phospholipid pools or feedback regulation via related lipid enzymes. For instance, Valproate indirectly increases PGS1 activity by lowering cellular inositol levels.