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. Author manuscript; available in PMC: 2015 Apr 1.
Published in final edited form as: Chem Phys Lipids. 2013 Nov 1;179:25–31. doi: 10.1016/j.chemphyslip.2013.10.008

FIGURE 1. The topology of CL biosythesis and remodeling.

FIGURE 1

Phosphatidic acid (PA) is synthesized in the ER and translocates to mitochondria in a process that is influenced by the ERMES (ER-mitochondria encounter structure) complex. Ups1/Mdm35p heterodimers transport PA from the OM to the IM, potentially at contact sites (established by MINOS/MICOS/MitOS complexes). PA is converted to CDP-diacylglycerol (CDP-DAG) by Tam41p on the matrix-facing leaflet of the IM. CDP-DAG is used to generate phosphatidylglycerolphosphate (PGP) by Pgs1p. PGP is dephosphorylated to phosphatidylglycerol (PG) by Gep4p. PG and another CDP-DAG are condensed to form unremodeled CL by Crd1p. CL is deacylated by Cld1p on the matrix-facing leaflet of the IM, forming MLCL. Via an unknown mechanism, MLCL must flip to the IMS-facing leaflet of the IM or be transported to the OM to gain access to the transacylase Taz1p, which regenerates CL. Multiple rounds of deacylation/reacylation result in remodeled CL which is enriched in unsaturated acyl chains. CL achieves its final distribution on both leaflets of the IM and OM through currently ill-defined mechanisms. The depicted topology of Pgs1p has not been experimentally verified. Solid lines indicate known pathways. Dashed lines delineate potential but currently unknown phospholipid transport processes.