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

doi:10.1016/j.devcel.2015.04.015

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

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	603-610
Number of pages	8
Journal	Developmental Cell
Volume	33
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2015.04.015
State	Published - 8 Jun 2015

All Science Journal Classification (ASJC) codes

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

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10.1016/j.devcel.2015.04.015

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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.",

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

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T1 - Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies

AU - Moldavski, Ofer

AU - Amen, T

AU - Levin-Zaidman, Smadar

AU - Eisenstein, Miriam

AU - Rogachev, Ilana

AU - Brandis, Alexander

AU - Kaganovich, Daniel

AU - Schuldiner, Maya

PY - 2015/6/8

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AB - 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.

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DO - 10.1016/j.devcel.2015.04.015

M3 - مقالة

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EP - 610

JO - Developmental Cell

JF - Developmental Cell

IS - 5

ER -

Lipid Droplets Are Essential for Efficient Clearance of Cytosolic Inclusion Bodies

Abstract

All Science Journal Classification (ASJC) codes

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