Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis

Author:

Jacome Burbano Maria Sol,Robin Jérôme D.ORCID,Bauwens Serge,Martin Marjorie,Donati Emma,Martínez LuciaORCID,Lin Peipei,Sacconi Sabrina,Magdinier Frédérique,Gilson EricORCID

Abstract

AbstractTelomeric repeat binding factor 2 (TRF2) binds to telomeres and protects chromosome ends against the DNA damage response and senescence. Although the expression of TRF2 is downregulated upon cellular senescence and in various aging tissues, including skeletal muscle tissues, very little is known about the contribution of this decline to aging. We previously showed that TRF2 loss in myofibers does not trigger telomere deprotection but mitochondrial dysfunction leading to an increased level of reactive oxygen species. We show here that this oxidative stress triggers the binding of FOXO3a to telomeres where it protects against ATM activation, revealing a previously unrecognized telomere protective function of FOXO3a, to the best of our knowledge. We further showed in transformed fibroblasts and myotubes that the telomere properties of FOXO3a are dependent on the C-terminal segment of its CR2 domain (CR2C) but independent of its Forkhead DNA binding domain and of its CR3 transactivation domain. We propose that these non-canonical properties of FOXO3a at telomeres play a role downstream of the mitochondrial signaling induced by TRF2 downregulation to regulate skeletal muscle homeostasis and aging.

Funder

Inserm Cross-cutting program AGEMED

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Molecular and Structural Alterations of Skeletal Muscle Tissue Nuclei during Aging;International Journal of Molecular Sciences;2024-02-02

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