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Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast

Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast
Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast

The division of the S. cerevisiae budding yeast, which produces one mother cell and one daughter cell, is asymmetric with respect to aging. Remarkably, the asymmetry of yeast aging coincides with asymmetric inheritance of damaged and aggregated proteins by the mother cell. Here, we show that misfolded proteins are retained in the mother cell by being sequestered in juxtanuclear quality control compartment (JUNQ) and insoluble protein deposit (IPOD) inclusions, which are attached to organelles. Upon exposure to stress, misfolded proteins accumulate in stress foci that must be disaggregated by Hsp104 in order to be degraded or processed to JUNQ and IPOD. Cells that fail to deliver aggregates to an inclusion pass on aggregates to subsequent generations.

Cell Division, Heat-Shock Proteins/metabolism, Organelles/metabolism, Protein Folding, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism
2211-1247
738-747
Spokoini, Rachel
44fad0b1-37be-44d8-9a4d-768b50e9011c
Moldavski, Ofer
a8e0c768-bef2-4be2-97d0-2dbacea308be
Nahmias, Yaakov
fadbfc9b-3ac4-4380-a10f-078bd616a4d4
England, Jeremy L
2f67b12b-9d45-4530-8d48-00034a22e9f9
Schuldiner, Maya
9cea7b6b-63b1-4170-91a8-abc11c8020df
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f
Spokoini, Rachel
44fad0b1-37be-44d8-9a4d-768b50e9011c
Moldavski, Ofer
a8e0c768-bef2-4be2-97d0-2dbacea308be
Nahmias, Yaakov
fadbfc9b-3ac4-4380-a10f-078bd616a4d4
England, Jeremy L
2f67b12b-9d45-4530-8d48-00034a22e9f9
Schuldiner, Maya
9cea7b6b-63b1-4170-91a8-abc11c8020df
Kaganovich, Daniel
ebb13f4e-e925-4aef-88e7-ddc25ef52d8f

Spokoini, Rachel, Moldavski, Ofer, Nahmias, Yaakov, England, Jeremy L, Schuldiner, Maya and Kaganovich, Daniel (2012) Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast. Cell Reports, 2 (4), 738-747. (doi:10.1016/j.celrep.2012.08.024).

Record type: Article

Abstract

The division of the S. cerevisiae budding yeast, which produces one mother cell and one daughter cell, is asymmetric with respect to aging. Remarkably, the asymmetry of yeast aging coincides with asymmetric inheritance of damaged and aggregated proteins by the mother cell. Here, we show that misfolded proteins are retained in the mother cell by being sequestered in juxtanuclear quality control compartment (JUNQ) and insoluble protein deposit (IPOD) inclusions, which are attached to organelles. Upon exposure to stress, misfolded proteins accumulate in stress foci that must be disaggregated by Hsp104 in order to be degraded or processed to JUNQ and IPOD. Cells that fail to deliver aggregates to an inclusion pass on aggregates to subsequent generations.

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More information

Accepted/In Press date: 21 August 2012
Published date: 25 October 2012
Additional Information: Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.
Keywords: Cell Division, Heat-Shock Proteins/metabolism, Organelles/metabolism, Protein Folding, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism

Identifiers

Local EPrints ID: 474258
URI: http://eprints.soton.ac.uk/id/eprint/474258
ISSN: 2211-1247
PURE UUID: 6b9f4525-2c25-42d3-9c3a-621738d309f4
ORCID for Daniel Kaganovich: ORCID iD orcid.org/0000-0003-2398-1596

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Date deposited: 16 Feb 2023 18:06
Last modified: 17 Mar 2024 04:17

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Contributors

Author: Rachel Spokoini
Author: Ofer Moldavski
Author: Yaakov Nahmias
Author: Jeremy L England
Author: Maya Schuldiner
Author: Daniel Kaganovich ORCID iD

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