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Roles for L o microdomains and ESCRT in ER stress-induced lipid droplet microautophagy in budding yeast

Pin-Chao Liao1, Enrique J Garcia1, Gary Tan1

  • 1Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.

Molecular Biology of the Cell
|October 20, 2021
PubMed

Insights

Microlipophagy (µLP), the direct engulfment of lipid droplets (LDs) by vacuoles, involves distinct mechanisms depending on the stressor. ER stress can induce Lo microdomains independently of ESCRT, revealing stressor-specific pathways in yeast.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Yeast Genetics

Background:

  • Microlipophagy (µLP) is an autophagosome-independent pathway for degrading lipid droplets (LDs) via direct lysosomal/vacuolar uptake.
  • In nutrient-limited yeast, µLP involves liquid-ordered (Lo) microdomains in vacuolar membranes and requires the Endosome Sorting Complex Required for Transport (ESCRT).
  • ESCRT has also been implicated in µLP induced by Endoplasmic Reticulum (ER) stressors or diauxic shift.

Purpose of the Study:

  • To investigate the mechanisms of µLP induced by ER stress, specifically focusing on the roles of Lo microdomains and ESCRT.
  • To determine if Lo microdomain formation and ESCRT function are conserved across different ER stress conditions.

Main Methods:

  • Induction of ER stress using lipid imbalance and other stressors in *Saccharomyces cerevisiae*.
  • Assessment of Lo microdomain formation and its dependence on ESCRT and Niemann-Pick type C sterol transfer proteins.
  • Inhibition of ESCRT or Lo microdomain formation to evaluate their impact on µLP.
  • Analysis of µLP induced by specific ER stressors (dithiothreitol, tunicamycin) and its relation to Lo microdomains and ESCRT.

Main Results:

  • ER stress induced by lipid imbalance triggers Lo microdomain formation in an ESCRT-independent manner, dependent on Niemann-Pick type C sterol transfer proteins.
  • Inhibition of either ESCRT or Lo microdomains partially reduced lipid imbalance-induced µLP, while combined inhibition abolished it.
  • ER stressors like dithiothreitol and tunicamycin induced µLP via an ESCRT-dependent, Lo microdomain-independent pathway.

Conclusions:

  • Lo microdomain formation is a general yeast stress response, but its induction mechanism is stressor-specific.
  • ESCRT and Lo microdomains play distinct, albeit sometimes overlapping, roles in LD uptake during stress-induced µLP.
  • These findings highlight the complexity and specificity of cellular stress responses in regulating lipid metabolism and degradation.

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