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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/174015
Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability
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Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome degradative function has been mainly studied in interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal instability, a hallmark of cancer. Heretofore, correct mitotic progression relies on the orchestrated degradation of mitotic factors, which was mainly attributed to ubiquitin-triggered proteasome-dependent degradation. Here, we show that mitotic transition does not only rely on proteasome-dependent degradation, as impairment of lysosomes increases mitotic timing and leads to mitotic errors, thus promoting chromosomal instability. Furthermore, we identified several putative lysosomal targets in mitotic cells. Among them, WAPL, a cohesin regulatory protein, emerged as a novel SQSTM1-interacting protein for targeted lysosomal degradation. Finally, we characterized an atypical nuclear phenotype, the toroidal nucleus, as a novel biomarker for genotoxic screenings. Our results establish lysosome-dependent degradation as an essential event to prevent chromosomal instability.
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ALMACELLAS I CANALS, Eugènia, et al. Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability. Autophagy. 2020. ISSN 1554-8627. [consulted: 10 of October of 2026]. Available at: https://hdl.handle.net/2445/174015