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. 2018 May 15;9(3):247–262. doi: 10.1093/advances/nmy007

FIGURE 2.

FIGURE 2

Biosynthesis of mature CL. Mature CL is largely synthesized in the IMM. Nascent CL is synthesized from PG by using CDP-DAG. The acyl chains of nascent CL are then modified to mature CL containing 4 linoleic acid acyl chains (18:2) with the enzyme TAZ. Nascent CL can also undergo acyl chain cleavage with PLA2 to produce MLCL, which can serve as a substrate for MLCLAT1 to produce mature CL. A small fraction of mature CL is produced in the endoplasmic reticulum membrane through the use of ALCAT1. For simplicity, biosynthesis of other key phospholipids is not depicted. These phospholipids (PC, PE, PS, PI, PG, and PA) are found in differing concentrations across the ER, OMM, and IMM. ALCAT1, acyl-CoA:lysocardiolipin acyltransferase 1; CDP-DAG, cytidinediphosphate-diacylglycerol; CL, cardiolipin; CRLS1, cardiolipin synthase; ER, endoplasmic reticulum; IMM, inner mitochondrial membrane; MAM, mitochondria-associated membrane; MLCL, monolyso-cardiolipin; MLCLAT1, monolyso-cardiolipin acyltransferase 1; OMM, outer mitochondrial membrane; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PLA2, phospholipase A2; PS, phosphatidylserine; TAZ, taffazin; (18:2)4CL, tetralinoleoyl cardiolipin.