| Autor: |
Chao Song, Wu Zheng, Guoming Liu, Yiyang Xu, Zhibo Deng, Yu Xiu, Rongsheng Zhang, Linhai Yang, Yifei Zhang, Guoyu Yu, Yibin Su, Jun Luo, Bingwei He, Jie Xu, Hanhao Dai |
| Jazyk: |
angličtina |
| Rok vydání: |
2025 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 79, Iss , Pp 103467- (2025) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2024.103467 |
| Popis: |
In aging and metabolic disease, sarcopenic obesity (SO) correlates with intramuscular adipose tissue (IMAT). Using bioinformatics analysis, we found a potential target protein Extended Synaptotagmin 1 (E-syt1) in SO. To investigate the regulatory role of E-syt1 in muscle metabolism, we performed in vivo and in vitro experiments through E-syt1 loss- and gain-of-function on muscle physiology. When E-syt1 is overexpressed in vitro, myoblast proliferation, differentiation, mitochondrial respiration, biogenesis, and mitochondrial dynamics are impaired, which were alleviated by the silence of E-syt1. Furthermore, overexpression of E-syt1 inhibited mitophagic flux. Mechanistically, E-syt1 overexpression leads to mitochondrial calcium overload and mitochondrial ROS burst, inhibits the fusion of mitophagosomes with lysosomes, and impedes the acidification of lysosomes. Animal experiments demonstrated the inhibition of E-syt1 increased the capacity of endurance exercise, muscle mass, mitochondrial function, and oxidative capacity of the muscle fibers in OVX mice. These findings establish E-syt1 as a novel contributor to the pathogenesis of skeletal muscle metabolic disorders in SO. Consequently, targeting E-syt1-induced dysfunction may serve as a viable strategy for attenuating SO. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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