Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence.
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
21 02 2019
21 02 2019
Historique:
received:
27
02
2018
revised:
15
11
2018
accepted:
09
01
2019
pubmed:
12
2
2019
medline:
7
1
2020
entrez:
12
2
2019
Statut:
ppublish
Résumé
Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging.
Identifiants
pubmed: 30739799
pii: S0092-8674(19)30051-0
doi: 10.1016/j.cell.2019.01.018
pmc: PMC6386581
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1083-1097.e18Subventions
Organisme : Wellcome Trust
ID : FC001203
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD085866
Pays : United States
Organisme : Wellcome Trust
ID : 110275/Z/15/Z
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA240765
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK098285
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG011085
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA217377
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM132447
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007287
Pays : United States
Organisme : Medical Research Council
ID : FC001203
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001203
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM046498
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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