THE PEL1 GENE (RENAMED PGS1) ENCODES THE PHOSPHATIDYLGLYCEROPHOSPHATESYNTHASE OF SACCHAROMYCES-CEREVISIAE

Phosphatidylglycerophosphate (PG-P) synthase catalyzes the synthesis o f PG-P from CDP-diacylglycerol and sn-glycerol 3-phosphate and functio ns as the committed and rate-limiting step in the biosynthesis of card iolipin (CL), In eukaryotic cells, CL is found predominantly in the in ner mitochondrial membrane and is generally thought to be an essential component of many mitochondrial functions. We have determined that th e PEL1 gene (now renamed PGS1), previously proposed to encode a second phosphatidylserine synthase of yeast (Janitor, M., Jarosch, E., Schwe yen, R. J., and Subik, J. (1995) Yeast 13, 1223-1231), in fact encodes a PG-P synthase of Saccharomyces cerevisiae, Overexpression of the PG S1 gene product under the inducible GAL1 promoter resulted in a 14-fol d increase in in vitro PG-P synthase activity. Disruption of the PGS1 gene in a haploid strain of yeast did not lead to a loss of viability but did result in a dependence on a fermentable carbon source for grow th, a temperature sensitivity for growth, and a petite lethal phenotyp e, The pgs1 null mutant exhibited no detectable in vitro PG-P synthase activity and no detectable CL or phosphatidylglycerol (PG); significa nt CL synthase activity was still present. The growth arrest phenotype and lack of PG-P synthase activity of a pgsA null allele of Escherich ia coil was corrected by an N-terminal truncated derivative of the yea st PG-P synthase, These results unequivocally demonstrate that the PGS 1 gene encodes the major PG-P synthase of yeast and that neither PG no r CL are absolutely essential for cell viability but may be important for normal mitochondrial function.