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Cited by 46Microtubule and mitosis dynamicsAutophagy in Disease and TherapyCellular transport and secretion

Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability

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Almacellas, Eugènia, Pelletier, Joffrey, Day, Charles, Ambrosio, Santiago, Tauler, Albert, Mauvezin, Caroline·2021·Autophagy
DOI 10.1080/15548627.2020.1764727PMC PMC8032240

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Abstract

ABSTRACT Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome function has mainly focused on 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 p62-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 genomic instability.

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  • Loss of optimal lysosomal activity disrupts cellular metabolism, leads to accumulation of undigested proteins, lipids and carbohydrates, and is linked to aging and age-related diseases such as Alzheimer's Disease.

    “Loss of optimal lysosomal activity profoundly disrupts cellular metabolism, leads to the accumulation of undigested proteins, lipids and carbohydrates, and is linked to aging and age-related diseases such as Alzheimer’s Disease.5”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [5]

    The Introduction describes lysosomes as degrading biological material, and the Results (Identification of novel lysosome substrates specifically during cell division; page unavailable) report protein accumulation after lysosomal inhibition. Our copy does not support the attributed claims about accumulated lipids or carbohydrates, profound disruption of cellular metabolism, or links to aging and Alzheimer’s disease. (LLM, conf=0.82)

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  • Possession of a single mutant allele responsible for certain childhood lysosomal disorders increases risk for a range of adult neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia and Parkinson's disease.

    “We now know that possession of a single mutant allele responsible for certain childhood disorders—those involving the lysosome—increases risk for a range of adult neurodegenerative disorders, including Alzheimer’s disease (AD), frontotemporal dementia (FTD) and Parkinson’s disease (PD).5,7”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [5]

    The Results and Discussion passages address lysosomal degradation during mitosis and chromosomal instability, not inherited lysosomal disorders or adult neurodegenerative risk. Searches for single mutant alleles, lysosomal disorders, and Alzheimer’s, frontotemporal dementia, and Parkinson’s disease found no passage in our copy supporting the claim. (LLM, conf=0.78)

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Cited by

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Authors
Almacellas, E., Pelletier, J., Day, C., Ambrosio, S., Tauler, A., & Mauvezin, C.
Affiliations
  • Institut d'Investigació Biomédica de Bellvitge (ES)
  • University of Minnesota (US)
  • Universitat de Barcelona (ES)
Corresponding author
  • Tauler, Albert
  • Mauvezin, Caroline
ORCID
Venue
Autophagy
Publisher
Informa UK Limited
Published
2020-06-23
Volume
17
Issue
3
Pages
796-813
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
DOI
10.1080/15548627.2020.1764727
PMC
PMC8032240
OpenAlex
W3036262519
Cited by
46
References
7
Citations by year
2026: 3 · 2025: 7 · 2024: 10 · 2023: 7 · 2022: 13 · 2021: 5 · 2020: 1
FWCI
3.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Autophagy (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
Funders
  • Agència de Gestió d’Ajuts Universitaris i de Recerca (2017SGR1743)
  • H2020 Marie Skłodowska-Curie Actions (799000)
  • Instituto de Salud Carlos III (RD12/0036/0049)
  • Ministerio de Ciencia, Innovación y Universidades (IJCI-2015-24716)
  • Ministerio de Economía, Industria y Competitividad, Gobierno de España (SAF2017-85561-R)
  • Ministerio de Educación, Cultura y Deporte (FPU13/05400)
  • National Institutes of Health (RO1-HL125353)
  • Mayo Clinic/National Institutes of Health training grant (5-T32-CA217836-02)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
lysosomal degradation, mitosis, chromosomal instability, WAPL, p62, cohesin, mitotic timing, genotoxicity biomarkers, mitotic errors, spindle assembly checkpoint, ubiquitin-proteasome system, cancer genomics, mitotic index
MeSH terms
Animals, Autophagy, Fibroblasts, HeLa Cells, Humans, Lysosomes, Mitosis, Transcription Factors, Ubiquitin, Chromosomal Instability, Proteasome Endopeptidase Complex

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