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oai:recercat.cat:2445/1789882025-12-04T19:32:57Zcom_2072_1057col_2072_478908col_2072_478917

urn:hdl:2445/178988 Proteostasis failure and mitochondrial dysfunction leads to aneuploidy-induced senescence Joy, Jery Barrio, Lara Santos Tapia, Celia Romão, Daniela Giakoumakis, Nikolaos Nikiforos Clemente Ruiz, Marta Milán, Marco Drosòfila Autofàgia Envelliment Cromosomes Drosophila Autophagy Aging Chromosomes 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. 2021-07-12T11:32:04Z 2022-07-02T05:10:19Z 2021-07-02 2021-07-12T10:31:47Z info:eu-repo/semantics/article Reproducció del document publicat a: https://doi.org/10.1016/j.devcel.2021.06.009 Developmental Cell, 2021, vol. 56, num. 14, p. 2043-2058.e7 https://doi.org/10.1016/j.devcel.2021.06.009 cc-by-nc-nd (c) Elsevier, 2021 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))