Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function |
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Authors: | Yue He Candice Yam Kyle Pomraning Jacqueline S R Chin Joanne Y Yew Michael Freitag Snezhana Oliferenko |
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Institution: | University of Chicago;aTemasek Life Sciences Laboratory, 117604 Singapore;bDepartment of Biological Sciences, National University of Singapore, 117543 Singapore;cDepartment of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331;dRandall Division of Cell and Molecular Biophysics, King''s College London, London SE1 1UL, United Kingdom |
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Abstract: | Excess fatty acids and sterols are stored as triacylglycerols and sterol esters in specialized cellular organelles, called lipid droplets. Understanding what determines the cellular amount of neutral lipids and their packaging into lipid droplets is of fundamental and applied interest. 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. |
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