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

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 demonstrated that SIRT7 promoted the glycolytic enzymes GBE1 and PYGL, suppressed the mitochondrial enzymes IDH1 and SDHB, and activated the RhoA/ROCK/AKT pathway and the EMT process, thereby facilitating the progression of endometriosis. CONCLUSIONS: These findings underscore the critical involvement of SIRT7 in the energy metabolism reprogramming of ectopic cells. Our research provides valuable insights for the development of nonsurgical treatment strategies for endometriosis.