Seipin is required for converting nascent to mature lipid droplets

• Published in: eLife Vol. 5
• Main Authors: Wang, Huajin, Becuwe, Michel, Housden, Benjamin E, Chitraju, Chandramohan, Porras, Ashley J, Graham, Morven M, Liu, Xinran N, Thiam, Abdou Rachid, Savage, David B, Agarwal, Anil K, Garg, Abhimanyu, Olarte, Maria-Jesus, Lin, Qingqing, Fröhlich, Florian, Hannibal-Bach, Hans Kristian, Upadhyayula, Srigokul, Perrimon, Norbert, Kirchhausen, Tomas, Ejsing, Christer S, Walther, Tobias C, Farese, Robert V
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 26-08-2016; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Biology; Cell Biology; Drosophila; endoplasmic reticulum; Enzymes; Fatty acids; Insects; Life Sciences; lipid droplet; Lipid metabolism; Lipids; LiveDrop; Mass spectrometry; Medical schools; Metabolic disorders; Morphology; Observations; organelle biogenesis; Protein-protein interactions; Scientific imaging; seipin; United States > US; lipid droplet; seipin; cell biology; lipid metabolism; LiveDrop; organelle biogenesis; D. melanogaster; human; endoplasmic reticulum
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.16582

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using
and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.