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Title:
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Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1
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Author:
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Moreno, David F.; Jenkins, Kirsten; Morlot, Sandrine; Charvin, Gilles; Csikász-Nagy, Attila; Aldea Malo, Martí
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Notes:
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Loss of proteostasis and cellular senescence are key hallmarks of aging, but direct
cause-effect relationships are not well understood. We show that most yeast cells arrest in G1
before death with low nuclear levels of Cln3, a key G1 cyclin extremely sensitive to chaperone
status. Chaperone availability is seriously compromised in aged cells, and the G1 arrest coincides
with massive aggregation of a metastable chaperone-activity reporter. Moreover, G1-cyclin
overexpression increases lifespan in a chaperone-dependent manner. As a key prediction of a
model integrating autocatalytic protein aggregation and a minimal Start network, enforced protein
aggregation causes a severe reduction in lifespan, an effect that is greatly alleviated by increased
expression of specific chaperones or cyclin Cln3. Overall, our data show that proteostasis
breakdown, by compromising chaperone activity and G1-cyclin function, causes an irreversible
arrest in G1, configuring a molecular pathway postulating proteostasis decay as a key contributing
effector of cell senescence. |
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Subject(s):
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-Marques de contrast
-Hallmarks
-Marcas de contraste
-Cells
-Células
-Cèl·lules
-Cln3
-61 |
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Rights:
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http://creativecommons.org/licenses/by-nc-nd/4.0/
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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Document type:
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Article
Article - Accepted version |
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Published by:
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eLife Sciences Publications
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Share:
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