Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies
Abstract: Targeting cellular senescence, one of the hallmarks of aging and aging‐related pathologies emerges as an effective strategy for anti‐aging and cancer chemotherapy. Here, a switch from TBK1‐OPTN axis to TBK1‐ATAD3A axis to promote cellular senescence is shown. Mechanically, TBK1 protein is abnormally activated and localized to the mitochondria during senescence, which directly phosphorylates ATAD3A at Ser321. Phosphorylated ATAD3A is significantly elevated in cellular senescence as well as in physiological and pathological aging and is essential for suppressing Pink1‐mediated mitophagy by facilitating Pink1 mitochondrial import. Inhibition of ATAD3A phosphorylation at Ser321 by either TBK1 deficiency or by a Ser321A mutation rescues the cellular senescence. A blocking peptide, TAT‐PEP, specifically abrogating ATAD3A phosphorylation, results in elevated cell death by preventing doxorubicin‐induced senescence, thus leading to enhanced tumor sensitivity to chemotherapy. TAT‐PEP treatment also ameliorates various phenotypes associated with physiological aging. Collectively, these results reveal the TBK1‐ATAD3A‐Pink1 axis as a driving force in cellular senescence and suggest a potential mitochondrial target for anti‐aging therapy.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies ; day:08 ; month:11 ; year:2024 ; extent:20
Advanced science ; (08.11.2024) (gesamt 20)
- Urheber
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He, Yujiao
Liu, Yanchen
Zheng, Mingyue
Zou, Yuxiu
Huang, Mujie
Wang, Linsheng
Gao, Ge
Zhou, Zhongjun
Jin, Guoxiang
- DOI
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10.1002/advs.202404109
- URN
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urn:nbn:de:101:1-2411091416192.126848265796
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:25 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- He, Yujiao
- Liu, Yanchen
- Zheng, Mingyue
- Zou, Yuxiu
- Huang, Mujie
- Wang, Linsheng
- Gao, Ge
- Zhou, Zhongjun
- Jin, Guoxiang
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