Lipid droplet biogenesis is spatially coordinated at ER-vacuole contacts under nutritional stress

EMBO Rep. 2018 Jan;19(1):57-72. doi: 10.15252/embr.201744815. Epub 2017 Nov 16.

Abstract

Eukaryotic cells store lipids in cytosolic organelles known as lipid droplets (LDs). Lipid droplet bud from the endoplasmic reticulum (ER), and may be harvested by the vacuole for energy during prolonged periods of starvation. How cells spatially coordinate LD production is poorly understood. Here, we demonstrate that yeast ER-vacuole contact sites (NVJs) physically expand in response to metabolic stress, and serve as sites for LD production. NVJ tether Mdm1 demarcates sites of LD budding, and interacts with fatty acyl-CoA synthases at the NVJ periphery. Artificially expanding the NVJ through over-expressing Mdm1 is sufficient to drive NVJ-associated LD production, whereas ablating the NVJ induces defects in fatty acid-to-triglyceride production. Collectively, our data suggest a tight metabolic link between nutritional stress and LD biogenesis that is spatially coordinated at ER-vacuole contact sites.

Keywords: endoplasmic reticulum; lipid droplet; membrane contact site; nuclear ER–vacuole junction; nutritional stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / metabolism
  • Acetic Acid / pharmacology
  • Cerulenin / pharmacology
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Acids / biosynthesis
  • Gene Expression Regulation, Fungal*
  • Glucose / deficiency
  • Glucose / pharmacology
  • Glycerol / metabolism
  • Glycerol / pharmacology
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Lipid Droplets / drug effects
  • Lipid Droplets / metabolism*
  • Lipid Droplets / ultrastructure
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Stress, Physiological*
  • Time-Lapse Imaging
  • Transformation, Genetic
  • Triglycerides / biosynthesis
  • Vacuoles / drug effects
  • Vacuoles / metabolism*
  • Vacuoles / ultrastructure

Substances

  • Culture Media
  • Fatty Acids
  • Intermediate Filament Proteins
  • MDM1 protein, S cerevisiae
  • Nvj1 protein, S cerevisiae
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • Triglycerides
  • Cerulenin
  • Fatty Acid Synthases
  • FAS1 protein, S cerevisiae
  • FAS2 protein, S cerevisiae
  • Coenzyme A Ligases
  • Faa1 protein, S cerevisiae
  • Glucose
  • Glycerol
  • Acetic Acid