Figure 2.

PE biosynthetic pathways at the ER–mitochondria interface in yeast. (1) Base exchange pathway. In the biosynthesis of PS, head group exchange with PE is mediated by PSS2 in mammals. The reverse reaction can also synthesize PE from PS in small amounts. In yeast, calcium mediates base exchange between PS and PE through poorly understood mechanisms. (2) Acylation of lyso-PE to PE. Ale1p is an acyl transferase that facilitates the conversion of lyso-PE to PE. (3) CDP-ethanolamine pathway or Kennedy pathway. Phosphoethanolamine (Eth-P) is generated by phosphorylation of ethanolamine (Eth) by ethanolamine kinase (Ek1p) or through degradation of sphingolipids by Dpl1p. Phosphoethanolamine and CTP are metabolized by CTP:phosphoethanolamine cytidylyltransferase (Ect1p in yeast, ET in mammals) to generate CDP-ethanolamine (CDP-Eth), which with 1,2-diacylglycerol ethanolamine phosphotransferase (Ept1p in yeast, ETP in mammals) undergoes a condensation reaction with DAG to form the final product, PE. (4) Phosphatidylserine decarboxylase pathway. Upon its synthesis, PS is transported from the MAM of the ER to the OM of mitochondria until it reaches the IM where Psd1p is located. EMC and ERMES may facilitate transfer of PS to the OM. The OM and IM of mitochondria are tethered by mitochondrial contact site and cristae organizing system (MICOS) structures (please refer to text for mammalian proteins that also serve tethering functions). Alternatively, PS can be transferred to mitochondrial membranes through the yeast vacoule facilitated by v-CLAMP membrane tethers. In the enzymatic step, Psd1p decarboxylates PS to generate PE that is integrated in mitochondrial membranes or exported to other locations in the cell. PE generated by any of these pathways can be converted to PC through the action of PE methyltransferases (Pem1p/Pem2p in yeast or PEMT in mammals).