A mutation in sphingolipid synthesis suppresses defects in yeast ergosterol metabolism

A mutation in an otherwise nonessential ERG2 gene is synthetically lethal when combined with mutations in two transcription factors encoded by the UPC2 and ECM22 genes. Employing UV mutagenesis, we isolated a suppressor of the triple mutant erg2delta upc2delta ecm22delta. The morpholine-resistant phenotype of the suppressor was used to identify the suppressor as a mutation in the ELO3 gene. In an expression study on tridemorph-containing medium, using the inducible GAL1 promoter fused to the ELO3 open reading frame, we demonstrated that suppression occurred only when ELO3 was not expressed. ELO3 encodes an enzyme involved in sphingolipid synthesis required for long-chain FA synthesis. Surprisingly, a deletion of ELO2, also required for the synthesis of sphingolipid-containing long-chain FA, did not suppress the erg2delta upc2delta ecm22delta triple mutant. The sterol composition of the upc2delta ecm22delta double mutant reflected regulation of the latter part of the ergosterol synthesis by the Upc2p and Ecm22p transcription factors. This study demonstrates a synergistic relationship between two lipid species, sterols and sphingolipids.