Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies

Ofer Moldavski, T Amen, Smadar Levin-Zaidman, Miriam Eisenstein, Ilana Rogachev, Alexander Brandis, Daniel Kaganovich, Maya Schuldiner

Research output: Contribution to journalArticlepeer-review

Abstract

Exposing cells to folding stress causes a subset of their proteins to misfold and accumulate in inclusion bodies (IBs). IB formation and clearance are both active processes, but little is known about their mechanism. To shed light on this issue, we performed a screen with over 4,000 fluorescently tagged yeast proteins for co-localization with a model misfolded protein that marks IBs during folding stress. We identified 13 proteins that co-localize to IBs. Remarkably, one of these IB proteins, the uncharacterized and conserved protein Iml2, exhibited strong physical interactions with lipid droplet (LD) proteins. Indeed, we here show that IBs and LDs are spatially and functionally linked. We further demonstrate a mechanism for IB clearance via a sterol-based metabolite emanating from LDs. Our findings therefore uncover a function for Iml2 and LDs in regulating a critical stage of cellular proteostasis.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalDevelopmental Cell
Volume33
Issue number5
DOIs
StatePublished - 8 Jun 2015

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • Molecular Biology
  • Cell Biology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies'. Together they form a unique fingerprint.

Cite this