Open Access4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis
Author(s) -
Yifang He,
Qianzhao Ji,
Zeming Wu,
Yusheng Cai,
Jian Yin,
Yiyuan Zhang,
Sheng Zhang,
Xiaoqian Liu,
Weiqi Zhang,
Guanghui Liu,
Si Wang,
Moshi Song,
Jing Qu
Publication year - 2022
Publication title -
protein and cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.973
H-Index - 63
eISSN - 1674-8018
pISSN - 1674-800X
DOI - 10.1093/procel/pwac037
Subject(s) - senescence , microbiology and biotechnology , stem cell , biology , mitochondrion , mesenchymal stem cell , ectopic expression , homeostasis , cell , cell culture , genetics
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.