Yuwen Luo, Jun Li, Yun Wang, Hejie Liu, Yizaitiguli Reyimjan, Qianyun Liang, Jie He, Jiachen Bai, Yuhan Wang, Xinhua Zou, Yaman Song, Yuanke Liu, Yidan Sun, Jiarui Luo, Haobo Hu, Yunpeng Hou, Xiangwei Fu
Lipid homeostasis is essential for oocyte quality and developmental competence, and uncoupling protein 1 (UCP1) has been identified as a critical regulator of lipid metabolism in oocytes. However, the downstream molecular mechanism by which UCP1 regulates lipid homeostasis remains unexplored. In this study, we demonstrate that UCP1 inhibition impairs oocyte developmental competence, accompanied by increased lipid accumulation, elevated oxidative stress, and disrupted mitochondrial function. Further investigation revealed that UCP1 inhibition markedly elevated mitochondrial calcium levels, which were associated with upregulation of the mitochondrial calcium uniporter (MCU). Functional inhibition of MCU with Ru360 reduced mitochondrial calcium accumulation and alleviated mitochondrial function, redox homeostasis, and lipid metabolic balance, ultimately improving oocyte developmental competence. These findings suggest that UCP1 regulates oocyte lipid homeostasis and developmental competence through MCU-dependent mitochondrial calcium uptake, establishing a mechanistic link between mitochondrial uncoupling, calcium homeostasis, and oocyte quality.