Cardiolipin biosynthesis

Li, G., Chen, S., Thompson, M.N. and Greenberg, M.L., New insights into the regulation of cardiolipin biosynthesis in yeast implications for Barth syndrome, Biochim Biophys Acta 1771 (2007) 432-441. 

Figure 5.1 Schematic iUuslTation of cardiolipin biosynthesis and remodeling pathways. Newly synthesized cardiolipin (CL) (immature or nascent CL) is formed by the condensation of phosphatidylglycerol (PG) and cytidine diphosphate-diacylglycerol (CDP-DAG) catalyzed by CL synthase. Immature CL is then deacylated to form monolysoCL and then reacylated using acyl chains from acyl CoA or Iransacylated from the sn-2 acyl chain of PC and PE species, leading to the formation of matured CL.

Phosphatidate Is the Common Precursor in the Biosynthesis of Triacylglycerols, Many Phosphoglycerols, Cardiolipin... 

In mammalian cells, the final stage of PS biosynthesis occurs in ER and MAM (Trotter and Voelker, 1994 Daum and Vance, 1997 Voelker, 2000). The other membranes in the ceU, such as mitochondria, nucleus, and plasma membrane, are therefore assembled from PS exported from ER and MAM (Figure 2). Phospholipid synthesis in mitochondria is restricted to the formation ofphosphatidylglycerol, cardiolipin, and PE, and other lipids such as PC and PS must be imported from sites of cellular lipid synthesis, ER or MAM (Daum, 1985 Vance, 1991). PS imported to the outer mitochondrial membrane is then translocated to the inner mitochondrial membrane, where it is converted to PE by PS decarboxylase (PSD) (Dennis and Kennedy, 1972 Voelker, 1990). It has been shown that the translocation of PS to mitochondria followed by its decarboxylation is a major pathway for the synthesis of PE in some cultured mammahan cells (Voelker, 1984 Kuge et al, 1986 Voelker and Frazier, 1986), suggesting that significant amounts of PE found in cell membranes are derived from mitochondria. 

The supply of lipids for mitochondrial membrane biosynthesis depends largely on lipids synthesized elsewhere in the cell, especially the endoplasmic reticulum. However, one major lipid component of the inner mitochondrial membrane, cardiolipin (diphosphatidylglycerol), is synthesized within the mitochondria. 

As with most mitochondrial proteins, biosynthesis occurs on micro-somes and GDH is then transported into mitochondria (79). The observed binding of GDH to phosphatidylserine, which in vivo is found in microsomal membranes, and to cardiolipin, which is found in mitochondrial membranes, has led to the suggestion, not as yet demonstrated experimentally, that these phospholipids are involved in transport (79,80). 

Higashi, Y. Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. XX. Identification of phosphatidylglycerol and cardiolipin as cofactors for isoprenoid alcohol phosphokinase. J. Biol. Chem., 245, 3691-3696 (1970)... 

Reddy, P.V., Schmid, PC., Natarajan, V., Schmid, H.H.O., 1983. The role of cardiolipin as an acyl donor in iV-acylethanolamine phospholipid biosynthesis. Biochim. Biophys. Acta 751, 241-246. 

Bisphosphatidylglycerol (BPG, cardiolipin) is concentrated in the mitochondrial inner membrane in plants (Table 1), as in animals. The pathway of biosynthesis is... 

Figure 7.1 The biosynthesis of some important phospholipids. PtdChol = Phosphatidylcholine PtdEth = Phosphatidylethanolamine PtdSer = Phosphatidylserine PtdGly = Phosphatidylglycerol DiPtdGly = DIphosphatidylglycerol [cardiolipin) ...

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