Autophagic removal of micronuclei
Open accessAbstract
Macroautophagy is known to participate in the quality control and turnover of cytoplasmic organelles, yet there is little evidence that macroautophagy targets nuclei in mammalian cells. Here, we investigated whether autophagy may target micronuclei, which arise as a result of deficient bipolar chromosome segregation in cells exposed to cell cycle perturbations. After removal of several distinct cell cycle blockers (nocodazole, cytochalasin D, hydroxyurea or SP600125), cells manifested an increase in the frequency of micronuclei (positive for histone H2B-RFP) as well as an increase in autophagic puncta (positive for GFP-LC3) over several days. A small but significant percentage of micronuclei co-localized with GFP-LC3 in autophagy-competent cells and this co-localization was lost after knockdown of ATG5 or ATG7. Electron microscopy analyses confirmed autophagic sequestration of micronuclei. "Autophagic micronuclei" (GFP-LC3⁺) were also decorated with p62/SQSTM1, while non-autophagic (GFP-LC3⁻) micronuclei where p62/SQSTM1 negative. In addition, GFP-LC3⁺ micronuclei exhibited signs of envelope degradation and γH2AX⁺ DNA damage foci, yet stained less intensively for chromatin markers, whereas GFP-LC3⁻ micronuclei were surrounded by an intact envelope and rarely exhibited markers or DNA damage. These results indicate that micronuclei can be subjected to autophagic degradation. Moreover, it can be speculated that removal of micronuclei may contribute to the genome-stabilizing effects of autophagy.
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Degradation by autophagy has been proposed for CCF and MN.
“Degradation by autophagy has also been proposed for CCF and MN (Dou et al., 2015; Rello-Varona et al., 2012; Sagona et al., 2014).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Rello-Varona et al., 2012
Autophagy destroys micronuclei arising from aberrant mitoses that perturb cell division and give rise to tetraploid cancer cell precursors.
“Autophagy destroys micronuclei that arise from aberrant mitoses and then perturb cell division, giving rise to tetraploid cancer cell precursors.154”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [154]
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Research works printed but not linked: 2
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Liu, D., Shaukat, Z., Xu, T., Denton, D., Saint, R. B., & Gregory, S. L. (2016) · Oncotarget · doi:10.18632/oncotarget.11736 · Cited by 32 · see citing works
STING signaling in inflammaging: a new target against musculoskeletal diseases
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HMGB1 promotes chemoresistance in small cell lung cancer by inducing PARP1-related nucleophagy
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p62/SQSTM1 in cancer: phenomena, mechanisms, and regulation in DNA damage repair
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Genetic elements promote retention of extrachromosomal DNA in cancer cells
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Nucleophagy—Implications for Microautophagy and Health
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Origins of chromosome instability unveiled by coupled imaging and genomics
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Mammalian nucleophagy: process and function
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- Authors
- Rello-Varona, S., Lissa, D., Shen, S., Niso-Santano, M., Senovilla, L., Mariño, G., Vitale, I., Jemaá, M., Harper, F., Pierron, G., Castedo, M., & Kroemer, G.
- Affiliations
- INSERM, U848; Institut Gustave Roussy; Université Paris Sud; Villejuif, France
- Université Paris-Sud (FR)
- Inserm (FR)
- ORCID
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2012-01-01
- Volume
- 11
- Issue
- 1
- Pages
- 170-176
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2008685892
- Cited by
- 198
- References
- 0
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 10 · 2023: 17 · 2022: 12 · 2021: 30 · 2020: 20 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 20 · 2015: 12 · 2014: 12 · 2013: 4 · 2012: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- Funders
- European Commission
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Institut National Du Cancer
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- autophagy, micronuclei, macroautophagy, ATG5, ATG7, p62, LC3, chromosome segregation errors, cell cycle inhibitors, DNA damage, genome stability
- MeSH terms
- Autophagy-Related Protein 5, Autophagy-Related Protein 7, Autophagy, Cell Nucleus, DNA Damage, Histones, Humans, Microtubule-Associated Proteins, Nuclear Envelope, Recombinant Fusion Proteins, RNA Interference, RNA, Small Interfering, Ubiquitin-Activating Enzymes, Cell Line, Tumor, Micronuclei, Chromosome-Defective
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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