eLife (Aug 2016)

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 Fröhlich,
  • Hans Kristian Hannibal-Bach,
  • Srigokul Upadhyayula,
  • Norbert Perrimon,
  • Tomas Kirchhausen,
  • Christer S Ejsing,
  • Tobias C Walther,
  • Robert V Farese Jr

DOI
https://doi.org/10.7554/eLife.16582
Journal volume & issue
Vol. 5

Abstract

Read online

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.

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