Lipid droplet biogenesis is spatially coordinated at ER–vacuole contacts under nutritional stress. (16th November 2017)

• Record Type: Journal Article
• Authors: Hariri, Hanaa; Rogers, Sean; Ugrankar, Rupali; Liu, Yang Lydia; Feathers, J Ryan; Henne, W Mike
• Is Part Of: EMBO reports. Volume 19:Number 1(2018)
• Page Start: 57
• Page End: 72
• Publication Date: 2017-11-16
• Subjects: endoplasmic reticulum -- lipid droplet -- membrane contact site -- nuclear ER–vacuole junction -- nutritional stress; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201744815
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: Under starvation conditions, yeast ER‐vacuole contact sites (NVJs) expand and become a site for lipid droplet (LD) biogenesis. The tethering protein, Mdm1, interacts with fatty acid activating enzymes and promotes NVJ‐associated LD production. NVJs expand in metabolically challenging conditions. Upregulation of NVJ1 is not sufficient to expand the NVJ. NVJs can be sites for LD budding. NVJ tether Mdm1 interacts with LDs at the NVJ periphery. Abstract : Under starvation conditions, yeast ER‐vacuole contact sites (NVJs) expand and become a site for lipid droplet (LD) biogenesis. The tethering protein, Mdm1, interacts with fatty acid activating enzymes and promotes NVJ‐associated LD production.