Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_61F53FCBFD55
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation.
Journal
Nature communications
Author(s)
Hämälistö S., Stahl J.L., Favaro E., Yang Q., Liu B., Christoffersen L., Loos B., Guasch Boldú C., Joyce J.A., Reinheckel T., Barisic M., Jäättelä M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
13/01/2020
Peer-reviewed
Oui
Volume
11
Number
1
Pages
229
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Lysosomes are membrane-surrounded cytoplasmic organelles filled with a powerful cocktail of hydrolases. Besides degrading cellular constituents inside the lysosomal lumen, lysosomal hydrolases promote tissue remodeling when delivered to the extracellular space and cell death when released to the cytosol. Here, we show that spatially and temporally controlled lysosomal leakage contributes to the accurate chromosome segregation in normal mammalian cell division. One or more chromatin-proximal lysosomes leak in the majority of prometaphases, after which active cathepsin B (CTSB) localizes to the metaphase chromatin and cleaves a small subset of histone H3. Stabilization of lysosomal membranes or inhibition of CTSB activity during mitotic entry results in a significant increase in telomere-related chromosome segregation defects, whereas cells and tissues lacking CTSB and cells expressing CTSB-resistant histone H3 accumulate micronuclei and other nuclear defects. These data suggest that lysosomal leakage and chromatin-associated CTSB contribute to proper chromosome segregation and maintenance of genomic integrity.
Keywords
Animals, Cathepsin B/antagonists & inhibitors, Cathepsin B/genetics, Cathepsin B/metabolism, Cell Line, Cell Nucleus/genetics, Cell Nucleus/pathology, Chromatin/metabolism, Chromosome Segregation/genetics, Female, Gene Silencing, Histones/metabolism, Humans, Intracellular Membranes/metabolism, Lysosomes/enzymology, Lysosomes/metabolism, Metaphase, Mice, Mitosis/genetics, Permeability, Telomere/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2020 17:14
Last modification date
27/04/2020 6:20
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