title: Synthetic lethal interaction of the mitochondrial phosphatidylethanolamine and cardiolipin biosynthetic pathways in Saccharomyces cerevisiae.
abstract: Saccharomyces cerevisiae mitochondria contain enzymes required for synthesis of the phospholipids cardiolipin (CL) and phosphatidylethanolamine (PE), which are enriched in mitochondrial membranes. Previous studies indicated that PE may compensate for the lack of CL, and vice versa. These data suggest that PE and CL have overlapping functions and that the absence of both lipids may be lethal. To address this hypothesis, we determined whether the crd1delta mutant, which lacks CL, was viable in genetic backgrounds in which PE synthesis was genetically blocked. Deletion of the mitochondrial PE pathway gene PSD1 was synthetically lethal with the crd1delta mutant, whereas deletion of the Golgi and endoplasmic reticulum pathway genes PSD2 and DPL1 did not result in synthetic lethality. A 20-fold reduction in phosphatidylcholine did not affect the growth of crd1delta cells. Supplementation with ethanolamine, which led to increased PE synthesis, or with propanolamine, which led to synthesis of the novel phospholipid phosphatidylpropanolamine, failed to rescue the synthetic lethality of the crd1delta psd1delta cells. These results suggest that mitochondrial biosynthesis of PE is essential for the viability of yeast mutants lacking CL.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
authors.forename: Vishal M
authors.initials: VM
authors.lastname: Gohil
authors.forename: Morgan N
authors.initials: MN
authors.lastname: Thompson
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Greenberg
mesh_terms: D002262:Carboxy-Lyases / Q000235:genetics* / Q000502:physiology*; D002308:Cardiolipins / Q000737:chemistry*; D049109:Cell Proliferation; D002470:Cell Survival; D017931:DNA Primers / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013997:Time Factors; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics* / Q000502:physiology*
chemical_list: D002308:Cardiolipins; D017931:DNA Primers; D008055:Lipids; D008565:Membrane Proteins; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C483858:phosphatidylethanolamine; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D002262:Carboxy-Lyases; C022353:phosphatidylserine decarboxylase