Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation

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Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. / Hämälistö, Saara; Stahl, Jonathan Lucien; Favaro, Elena; Yang, Qing; Liu, Bin; Christoffersen, Line; Loos, Ben; Guasch Boldú, Claudia; Joyce, Johanna A.; Reinheckel, Thomas; Barisic, Marin; Jäättelä, Marja.

In: Nature Communications, Vol. 11, No. 1, 229, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Hämälistö, S, Stahl, JL, Favaro, E, Yang, Q, Liu, B, Christoffersen, L, Loos, B, Guasch Boldú, C, Joyce, JA, Reinheckel, T, Barisic, M & Jäättelä, M 2020, 'Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation', Nature Communications, vol. 11, no. 1, 229. https://doi.org/10.1038/s41467-019-14009-0

APA

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. (2020). Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. Nature Communications, 11(1), [229]. https://doi.org/10.1038/s41467-019-14009-0

Vancouver

Hämälistö S, Stahl JL, Favaro E, Yang Q, Liu B, Christoffersen L et al. Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. Nature Communications. 2020;11(1). 229. https://doi.org/10.1038/s41467-019-14009-0

Author

Hämälistö, Saara ; Stahl, Jonathan Lucien ; Favaro, Elena ; Yang, Qing ; Liu, Bin ; Christoffersen, Line ; Loos, Ben ; Guasch Boldú, Claudia ; Joyce, Johanna A. ; Reinheckel, Thomas ; Barisic, Marin ; Jäättelä, Marja. / Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{b4e171a4275a444e869265115a406863,
title = "Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation",
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.",
author = "Saara H{\"a}m{\"a}list{\"o} and Stahl, {Jonathan Lucien} and Elena Favaro and Qing Yang and Bin Liu and Line Christoffersen and Ben Loos and {Guasch Bold{\'u}}, Claudia and Joyce, {Johanna A.} and Thomas Reinheckel and Marin Barisic and Marja J{\"a}{\"a}ttel{\"a}",
year = "2020",
doi = "10.1038/s41467-019-14009-0",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Spatially and temporally defined lysosomal leakage facilitates mitotic chromosome segregation

AU - Hämälistö, Saara

AU - Stahl, Jonathan Lucien

AU - Favaro, Elena

AU - Yang, Qing

AU - Liu, Bin

AU - Christoffersen, Line

AU - Loos, Ben

AU - Guasch Boldú, Claudia

AU - Joyce, Johanna A.

AU - Reinheckel, Thomas

AU - Barisic, Marin

AU - Jäättelä, Marja

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-14009-0

DO - 10.1038/s41467-019-14009-0

M3 - Journal article

C2 - 31932607

AN - SCOPUS:85077786017

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 229

ER -

ID: 234637406