Figure 1.

Biochemical pathways for PE, PC, and CL biosynthesis in the yeast S. cerevisiae. CL biosynthesis occurs exclusively in the mitochondria, where Crd1 synthesizes nascent CL_p from PG. The resulting CL_p is deacylated by the phospholipase Cld1 to produce monolysocardiolipin (MLCL), which is then reacylated by the transacylase Taz1 to form mature cardiolipin (CL_m). Mutations in the human homologue of TAZ1 result in Barth syndrome. CL biosynthesis depends on the import of PA from endoplasmic reticulum, which is converted to CDP-DAG by Tam41. Pgs1 catalyzes conversion of CDP-DAG to PGP, which is then dephosphorylated to PG by Gep4. PE biosynthesis in yeast can occur by the following: 1) Psd1-catalyzed decarboxylation of PS in the mitochondria; 2) incorporation of Etn via the cytosolic/endoplasmic reticulum Kennedy pathway enzymes Eki1, Ect1, and Ept1, respectively; and 3) the acylation of lyso-PE by Ale1. The Kennedy pathway enzymes Cki1, Pct1, and Cpt1 can utilize choline to biosynthesize PC, a bilayer-forming phospholipid that is imported into mitochondria. CL_p, precursor cardiolipin; CL_m, mature cardiolipin; PG, phosphatidylglycerol; PGP, phosphatidylglycerol phosphate; CDP, cytidine diphosphate; DAG, diacylglycerol.