TFEB-dependent lysosome biogenesis is required for senescence

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TFEB-dependent lysosome biogenesis is required for senescence. / Curnock, Rachel; Yalci, Katy; Palmfeldt, Johan; Jäättelä, Marja; Liu, Bin; Carroll, Bernadette.

I: EMBO Journal, Bind 42, e111241, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Curnock, R, Yalci, K, Palmfeldt, J, Jäättelä, M, Liu, B & Carroll, B 2023, 'TFEB-dependent lysosome biogenesis is required for senescence', EMBO Journal, bind 42, e111241. https://doi.org/10.15252/embj.2022111241

APA

Curnock, R., Yalci, K., Palmfeldt, J., Jäättelä, M., Liu, B., & Carroll, B. (2023). TFEB-dependent lysosome biogenesis is required for senescence. EMBO Journal, 42, [e111241]. https://doi.org/10.15252/embj.2022111241

Vancouver

Curnock R, Yalci K, Palmfeldt J, Jäättelä M, Liu B, Carroll B. TFEB-dependent lysosome biogenesis is required for senescence. EMBO Journal. 2023;42. e111241. https://doi.org/10.15252/embj.2022111241

Author

Curnock, Rachel ; Yalci, Katy ; Palmfeldt, Johan ; Jäättelä, Marja ; Liu, Bin ; Carroll, Bernadette. / TFEB-dependent lysosome biogenesis is required for senescence. I: EMBO Journal. 2023 ; Bind 42.

Bibtex

@article{e711a12921a641ca93933ade706d70b9,

title = "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.",

keywords = "autophagy, lysosome, senescence, TFEB",

author = "Rachel Curnock and Katy Yalci and Johan Palmfeldt and Marja J{\"a}{\"a}ttel{\"a} and Bin Liu and Bernadette Carroll",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY 4.0 license.",

year = "2023",

doi = "10.15252/embj.2022111241",

language = "English",

volume = "42",

journal = "E M B O Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - TFEB-dependent lysosome biogenesis is required for senescence

AU - Curnock, Rachel

AU - Yalci, Katy

AU - Palmfeldt, Johan

AU - Jäättelä, Marja

AU - Liu, Bin

AU - Carroll, Bernadette

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - autophagy

KW - lysosome

KW - senescence

KW - TFEB

U2 - 10.15252/embj.2022111241

DO - 10.15252/embj.2022111241

M3 - Journal article

C2 - 36970883

AN - SCOPUS:85150800453

VL - 42

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

M1 - e111241

ER -

ID: 341345811