TFEB ‐dependent lysosome biogenesis is required for senescence
Abstract: The accumulation of senescent cells is recognised as a driver of tissue and organismal ageing. One of the gold‐standard hallmarks of a senescent cell is an increase in lysosomal content, as measured by senescence‐associated β‐galactosidase (Senβ‐Gal) activity. The lysosome plays a central role in integrating mitogenic and stress cues to control cell metabolism, which is known to be dysregulated in senescence. Despite this, little is known about the cause and consequence of lysosomal biogenesis in senescence. We find here that lysosomes in senescent cells are dysfunctional; they have higher pH, increased evidence of membrane damage and reduced proteolytic capacity. The significant increase in lysosomal content is however sufficient to maintain degradative capacity of the cell to a level comparable to proliferating control cells. We demonstrate that increased nuclear TFEB/TFE3 supports lysosome biogenesis, is a hallmark of multiple forms of senescence and is required for senescent cell survival. TFEB/TFE3 are hypo‐phosphorylated and show constitutive nuclear localisation in senescence. Evidence suggests that several pathways may contribute to TFEB/TFE3 dysregulation in senescence.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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TFEB ‐dependent lysosome biogenesis is required for senescence ; day:27 ; month:03 ; year:2023 ; extent:15
The EMBO journal / European Molecular Biology Organization ; (27.03.2023) (gesamt 15)
- Creator
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Curnock, Rachel
Yalci, Katy
Palmfeldt, Johan
Jäättelä, Marja
Liu, Bin
Carroll, Bernadette
- DOI
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10.15252/embj.2022111241
- URN
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urn:nbn:de:101:1-2023032715142576465125
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:55 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Curnock, Rachel
- Yalci, Katy
- Palmfeldt, Johan
- Jäättelä, Marja
- Liu, Bin
- Carroll, Bernadette
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