SIRT7 drives energy metabolic shifts in endometriosis via interaction with TUFM and Rhoa/Rock/Akt pathway activation

作者：Huaying Zhang, Jiahao Chen, Mengjie Yang, Xinyu Ding, Guolin Chai, Ruofan Huang, Dianchao Lin, Zhixiong Huang, Qionghua Chen · 发表于：Cellular and Molecular Life Sciences · 年份：2025 · DOI：10.1007/s00018-025-05886-4 · 被引用次数：3 · 研究领域：Sirtuins and Resveratrol in Medicine、Endometriosis Research and Treatment、Reproductive Biology and Fertility

PURPOSE: Endometriosis is characterized by the ectopic growth of endometrial-like tissue outside the uterus and altered energy metabolism, but the specific mechanisms involved remain unclear. This study aimed to investigate the impact of Sirtuins7 (SIRT7) on metabolic homeostasis to better understand the metabolic alterations underlying endometriosis. METHODS: Integrated metabolomic, transcriptomic, and proteomic analyses revealed metabolic dysregulation in endometriosis. Seahorse XF technology was used to assess metabolic rates. The effects of SIRT7 on endometriosis were validated both in vitro and in vivo. Immunoprecipitation and mass spectrometry were used to identify the interaction between SIRT7 and Tu translation elongation factor, mitochondrial (TUFM). Cellular phenotypes, including proliferation, migration, and apoptosis, were evaluated by CCK-8 assays, Transwell and scratch assays, and flow cytometry. RESULTS: Multiomics analyses and Seahorse XF tests revealed a metabolic shift from mitochondrial respiration to glycolysis in ectopic tissues. SIRT7 was found to be upregulated in ectopic lesions and significantly influenced the progression of endometriosis. In addition, an interaction between SIRT7 and TUFM has been observed. The metabolic reprogramming, proliferation and migration ability of endometrial stromal cells were greatly reduced by SIRT7 knockdown and TUFM overexpression. The effects of TUFM deficiency were reversed by SIRT7 knockdown. The results also demons...