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http://hdl.handle.net/2445/178988
Title: | Proteostasis failure and mitochondrial dysfunction leads to aneuploidy-induced senescence |
Author: | Joy, Jery Barrio, Lara Santos Tapia, Celia Romão, Daniela Giakoumakis, Nikolaos Nikiforos Clemente Ruiz, Marta Milán, Marco |
Keywords: | Drosòfila Autofàgia Envelliment Cromosomes Drosophila Autophagy Aging Chromosomes |
Issue Date: | 2-Jul-2021 |
Abstract: | Aneuploidy, an unbalanced number of chromosomes, is highly deleterious at the cellular level and leads to senescence, a stress-induced response characterized by permanent cell-cycle arrest and a well-defined associated secretory phenotype. Here, we use a Drosophila epithelial model to delineate the pathway that leads to the induction of senescence as a consequence of the acquisition of an aneuploid karyotype. Whereas aneuploidy induces, as a result of gene dosage imbalance, proteotoxic stress and activation of the major protein quality control mechanisms, near-saturation functioning of autophagy leads to compromised mitophagy, accumulation of dysfunctional mitochondria, and the production of radical oxygen species (ROS). We uncovered a role of c-Jun N-terminal kinase (JNK) in driving senescence as a consequence of dysfunctional mitochondria and ROS. We show that activation of the major protein quality control mechanisms and mitophagy dampens the deleterious effects of aneuploidy, and we identify a role of senescence in proteostasis and compensatory proliferation for tissue repair. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.devcel.2021.06.009 |
It is part of: | Developmental Cell, 2021, vol. 56, num. 14, p. 2043-2058.e7 |
URI: | http://hdl.handle.net/2445/178988 |
Related resource: | https://doi.org/10.1016/j.devcel.2021.06.009 |
ISSN: | 1534-5807 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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12541_6519885_jery_et_al_dev_cel_2021.pdf | 5.23 MB | Adobe PDF | View/Open |
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