Seipin is required for converting nascent to mature lipid droplets

Huajin Wang, Michel Becuwe, Benjamin E. Housden, Chandramohan Chitraju, Ashley J. Porras, Morven M. Graham, Xinran N. Liu, Abdou Rachid Thiam, David B. Savage, Anil K. Agarwal, Abhimanyu Garg, Maria Jesus Olarte, Qingqing Lin, Florian Frohlich, Hans Kristian Hannibal-Bach, Srigokul Upadhyayula, Norbert Perrimon, Tomas Kirchhausen, Christer S. Ejsing, Tobias C. WaltherRobert V. Farese

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila 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.

Original languageEnglish (US)
Article numbere16582
JournaleLife
Volume5
Issue numberAUGUST
DOIs
StatePublished - Aug 26 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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