Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy

Sarah Ouahoud, Mitchell D Fiet, Fernando Martínez-Montañés, Christer S Ejsing, Oliver Kuss, Michael Roden, Daniel F Markgraf*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Lipid droplets (LDs) store neutral lipids and are integrated into a cellular metabolic network that relies on functional coupling with various organelles. Factors mediating efficient coupling and mechanisms regulating them remain unknown. Here, we conducted a global screen in S. cerevisiae to identify genes required for the functional coupling of LDs and other organelles during LD consumption. We show that LD utilization during growth resumption is coupled to vacuole homeostasis. ESCRT-, V-ATPase- and vacuole protein sorting-mutants negatively affect LD consumption, independent of lipophagy. Loss of ESCRT function leads to the accumulation of LD-derived diacylglycerol (DAG), preventing its conversion into phosphatidic acid (PA) and membrane lipids. In addition, channeling of DAG from LD-proximal sites to the vacuole is blocked. We demonstrate that utilization of LDs requires intact vacuolar signaling via TORC1 and its downstream effector Sit4p. These data suggest that vacuolar status is coupled to LD catabolism via TORC1-mediated regulation of DAG-PA interconversion and explain how cells coordinate organelle dynamics throughout cell growth.

Original languageEnglish
Article numberjcs213876
JournalJournal of Cell Science
Volume131
Number of pages15
ISSN0021-9533
DOIs
Publication statusPublished - 11. Jun 2018

Keywords

  • Diacylglycerol
  • ESCRT
  • Lipid droplet
  • Lipid metabolism
  • TORC1
  • Vacuole homeostasis

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