Figure 1. Biosyntheses and functional relevance of mitochondrial membrane phospholipids.
A. PC and PE syntheses by the Kennedy pathway. Choline or ethanolamine undergoes sequential reactions with ATP, CTP, and DAG to produce PC or PE. The first two reactions are mediated by cytosolic enzymes, while the final steps involving DAG are mediated by enzymes that are embedded in the ERM.
B. Phospho-headgroup modifications of PC, PE, and PS mediated by PEMT, PSS1, and PSS2. PEMT is located at ERM/MAM, whereas PSS1/PSS2 are located at MAM.
C. Mitochondrial synthesis of PE by PSD at IMM.
D. Mitochondrial CL synthesis by CLS, tafazzin, PL-A2, and MLCLAT-1. Nascent CL molecules produced by CLS are subsequently de/re-acylated to form mature and functional CL.
E. Small quantity of CL can be synthesized on the ERM by ALCAT-1.
F. PI synthesis by CDS and PI synthase on the ERM. Molecules synthesized in ERM, OMM and IMM can be transported at MAM or intra-mitochondrial contact site.
Abbreviations: ALCAT-1 (acyl-CoA: lysocardiolipin acyltransferase-1), c (cytochrome c oxidase), CDS (CDP-DAG synthase), CK (choline kinase), CL (cardiolipin), CLS (cardiolipin synthase), CPT (CDP-choline phosphotransferase), CT (CTP:phosphocholine cytidylyltransferase), DAG (diacylglycerol), Eth (ethanolamine), EK (ethanolamine kinase), ERM (endoplasmic reticulum membrane), EPT (CDP-ethanolamine phosphotransferase), ET (CTP:phosphoethanolamine cytidylyltransferase), ETS (electron transport system), IMM (inner mitochondrial membrane), MAM (mitochondrial associated membrane), M-I (myo-inositol), MLCLAT-1 (monolysocardiolipin acyltransferase-1), OMM (outer mitochondrial membrane), PA (phosphatidic acid), PC (phosphatidylcholine), PE (phosphatidylethanolamine), PEMT (phosphatidylethanolamine N-methyltransferase), PG (phosphatidylglycerol), PI (phosphatidylinositol), PL-A2 (phospholipase-A2), PS (phosphatidylserine), PSD (phosphatidylserine decarboxylase), PSS1/2 (phosphatidylserine synthase 1/2), Q (co-enzyme Q10).