Joy, JeryBarrio, LaraSantos Tapia, CeliaRomão, DanielaGiakoumakis, Nikolaos NikiforosClemente Ruiz, MartaMilán, Marco2021-07-122022-07-022021-07-021534-5807https://hdl.handle.net/2445/178988Aneuploidy, 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.67 p.application/pdfengcc-by-nc-nd (c) Elsevier, 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/DrosòfilaAutofàgiaEnvellimentCromosomesDrosophilaAutophagyAgingChromosomesinfo:eu-repo/semantics/article2021-07-12info:eu-repo/semantics/openAccess6519885