Elina IKONEN, University of Helsinki, Finland

Elina IKONEN, PhD, invited by Xavier Prieur (Eq IV)
Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland
https://www.helsinki.fi/en/researchgroups/lipid-trafficking-lab

 

Abstract

Lipid droplets (LDs) are ubiquitous intracellular organelles, consisting of a core of neutral lipids surrounded by a phospholipid monolayer. Their main function is to store energy in times of excess and release it when needed. During LD formation, it is postulated that neutral lipids first accumulate within the endoplasmic reticulum (ER) bilayer in spatially restricted subdomains and then bud off into the cytoplasm as nascent LDs. Seipin is a homo-oligomeric ER membrane protein of unknown molecular function, implicated in LD biogenesis and mutated in severe congenital lipodystrophy (BSCL2). We have previously shown that seipin is crucial for the early steps of LD formation in human cells, with seipin complexes accumulating at nascent ER-LD contact sites, enabling their growth (Salo VT et al., EMBO J 2016). We used CRISPR/Cas9–mediated endogenous tagging of seipin and other key LD proteins in combination with live cell imaging and correlative light electron microscopy to characterize the LD formation and ER-LD contact sites in human cells. We also relocalized endogenous seipin in the ER network to study if this affects LD formation, and removed endogenous seipin from existing LDs, to address if seipin is needed at ER-LD contacts after LDs have formed. Our results suggest that seipin can define the site of LD formation, that seipin mediates the formation of ER-LD necks with a uniform architecture and that seipin is needed for the maintenance of LDs.