Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1
Author
Moreno, David F.
Jenkins, Kirsten
Morlot, Sandrine
Charvin, Gilles
Csikász-Nagy, Attila
Aldea Malo, Martí
Publication date
2019-09-13ISSN
2050-084X
Abstract
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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
61 - Medicina
Keywords
Marques de contrast
Hallmarks
Marcas de contraste
Cells
Células
Cèl·lules
Cln3
Pages
27
Publisher
eLife Sciences Publications
Collection
8;
Is part of
eLife
Citation
Moreno, David F.; Jenkins, Kirsten; Morlot, Sandrine; Charvin, Gilles; Csikasz-Nagy, Attila; Aldea Malo, Martí. «Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1». eLife, 2019, vol. 8, art. e48240. Disponible: <https://elifesciences.org/articles/48240>. Fecha de acceso: 25 oct. 2019. DOI: 10.7554/eLife.48240.034
This item appears in the following Collection(s)
- Ciències de la Salut [532]
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