Endonucleosis mediates internalization of cytoplasm into the nucleus

Ourania Galanopoulou, Evangelia C. Tachmatzidi, Elena Deligianni, Dimitris Botskaris, Kostas C. Nikolaou, Sofia Gargani, Yannis Dalezios, Georges Chalepakis and Iannis Talianidis ()
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Ourania Galanopoulou: Foundation for Research and Technology Hellas
Evangelia C. Tachmatzidi: Foundation for Research and Technology Hellas
Elena Deligianni: Foundation for Research and Technology Hellas
Dimitris Botskaris: Foundation for Research and Technology Hellas
Kostas C. Nikolaou: Biomedical Sciences Research Center Alexander Fleming
Sofia Gargani: Biomedical Sciences Research Center Alexander Fleming
Yannis Dalezios: School of Medicine University of Crete
Georges Chalepakis: Dept. of Biology University of Crete
Iannis Talianidis: Foundation for Research and Technology Hellas

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Setd8 regulates transcription elongation, mitotic DNA condensation, DNA damage response and replication licensing. Here we show that, in mitogen-stimulated liver-specific Setd8-KO mice, most of the hepatocytes are eliminated by necrosis but a significant number of them survive via entering a stage exhibiting several senescence-related features. Setd8-deficient hepatocytes had enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles surrounded by nuclear lamina. These vesicles contain glycogen, cytoplasmic proteins and even entire organelles. We term this process “endonucleosis”. Intranuclear vesicles are absent in hepatocytes of Setd8/Atg5 knockout mice, suggesting that the process requires the function of the canonical autophagy machinery. Endonucleosis and hyperploidization are temporary, early events in the surviving Setd8-deficient cells. Larger vesicles break down into microvesicles over time and are eventually eliminated. The results reveal sequential events in cells with extensive DNA damage, which function as part of survival mechanisms to prevent necrotic death.

Date: 2024
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DOI: 10.1038/s41467-024-50259-3

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