Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function.
Bottom Line: Using two species of fission yeast, we show that cycling cells deficient in the function of the ER-resident CDP-DG synthase Cds1 exhibit markedly increased triacylglycerol content and assemble large lipid droplets closely associated with the ER membranes.We demonstrate that these unusual structures recruit the triacylglycerol synthesis machinery and grow by expansion rather than by fusion.Our results suggest that interfering with the CDP-DG route of phosphatidic acid utilization rewires cellular metabolism to adopt a triacylglycerol-rich lifestyle reliant on the Kennedy pathway.
Affiliation: Temasek Life Sciences Laboratory, 117604 Singapore Department of Biological Sciences, National University of Singapore, 117543 Singapore.Show MeSH
Mentions: We sought to identify the mutation underlying the bbl1 phenotype using a whole-genome resequencing approach (see Materials and Methods for experimental details). Two adjacent CC nucleotides in the SJAG_00426.4 open reading frame (ORF) were found mutated to TT, which resulted in substitution of the evolutionarily conserved proline 363 residue to serine (P363S; Figure 3A and Supplemental Figure S3A). SJAG_00426.4 encodes a lipid biosynthesis enzyme from the CDP-DG synthase family highly conserved across all domains of life (Figure 3A and Supplemental Figure S3B). The budding yeast S. cerevisiae orthologue of SJAG_00426.4 is known as Cds1 (Shen et al., 1996).
Affiliation: Temasek Life Sciences Laboratory, 117604 Singapore Department of Biological Sciences, National University of Singapore, 117543 Singapore.