Seipin Facilitates Triglyceride Flow to Lipid Droplet and Counteracts Droplet Ripening via Endoplasmic Reticulum Contact

  • Dev Cell. 2019 Aug 19;50(4):478-493.e9. doi: 10.1016/j.devcel.2019.05.016.
Veijo T Salo  1 ,  Shiqian Li  1 ,  Helena Vihinen  2 ,  Maarit Hölttä-Vuori  1 ,  Abel Szkalisity  3 ,  Peter Horvath  3 ,  Ilya Belevich  2 ,  Johan Peränen  1 ,  Christoph Thiele  4 ,  Pentti Somerharju  5 ,  Hongxia Zhao  2 ,  Alexandre Santinho  6 ,  Abdou Rachid Thiam  7 ,  Eija Jokitalo  8 ,  Elina Ikonen  9
Affiliations
  • 1. Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
  • 2. Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
  • 3. Biological Research Center, Szeged, Hungary.
  • 4. Limes Institute, University of Bonn, Bonn, Germany.
  • 5. Department of Biochemistry, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • 6. Laboratoire de Physique de l'Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Universite de Paris, Paris, France.
  • 7. Laboratoire de Physique de l'Ecole Normale Supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Universite de Paris, Paris, France. Electronic address: [email protected].
  • 8. Institute of Biotechnology, University of Helsinki, Helsinki, Finland. Electronic address: [email protected].
  • 9. Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland. Electronic address: [email protected].
PMID: 31178403 DOI: 10.1016/j.devcel.2019.05.016
Abstract

Seipin is an oligomeric integral endoplasmic reticulum (ER) protein involved in lipid droplet (LD) biogenesis. To study the role of seipin in LD formation, we relocalized it to the nuclear envelope and found that LDs formed at these new seipin-defined sites. The sites were characterized by uniform seipin-mediated ER-LD necks. At low seipin content, LDs only grew at seipin sites, and tiny, growth-incompetent LDs appeared in a Rab18-dependent manner. When seipin was removed from ER-LD contacts within 1 h, no lipid metabolic defects were observed, but LDs became heterogeneous in size. Studies in seipin-ablated cells and model membranes revealed that this heterogeneity arises via a biophysical ripening process, with triglycerides partitioning from smaller to larger LDs through droplet-bilayer contacts. These results suggest that seipin supports the formation of structurally uniform ER-LD contacts and facilitates the delivery of triglycerides from ER to LDs. This counteracts ripening-induced shrinkage of small LDs.

Keywords
auxin-induced degradation; correlative light electron microscopy; electron tomography; lipid trafficking; lipogenesis; membrane contacts; model membranes; neutral lipid; organelle biogenesis; triglyceride.