4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis
Protein & Cell
;
(12): 202-216, 2023.
Artigo
em Inglês
| WPRIM
| ID: wpr-982531
ABSTRACT
Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Células Cultivadas
/
Senescência Celular
/
Complexo III da Cadeia de Transporte de Elétrons
/
Proteínas de Ciclo Celular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Células-Tronco Mesenquimais
/
Homeostase
/
Mitocôndrias
Limite:
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2023
Tipo de documento:
Artigo
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