title: Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies.
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.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Moldavski
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Triana
authors.initials: T
authors.lastname: Amen
authors.affiliation: Electron Microscopy Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Levin-Zaidman
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Eisenstein
authors.affiliation: Department for Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Rogachev
authors.affiliation: Department for Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brandis
authors.affiliation: Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address: dan@cc.huji.ac.il.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kaganovich
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: maya.schuldiner@weizmann.ac.il.
authors.forename: Maya
authors.initials: M
authors.lastname: Schuldiner
mesh_terms: D002468:Cell Physiological Phenomena; D003600:Cytosol / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D047468:Immunoprecipitation; D002479:Inclusion Bodies / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols