Zhou Dan, Zhuan Qingrui, Luo Yuwen, Liu Hongyu, Meng Lin, Du Xingzhu, Wu Guoquan, Hou Yunpeng, Li Jun, Fu Xiangwei
Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science, Beijing, 100193, China.
State Key Laboratories of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Theriogenology. 2022 Jul 15;187:205-214. doi: 10.1016/j.theriogenology.2022.05.006. Epub 2022 May 16.
Mitochondrial thermogenesis is an adaptive response of cells to their surrounding stress. Oxidative stress is one of the common stresses during in vitro maturation (IVM) of oocytes, which leads to mitochondrial dysfunction. This study aimed to probe the effects of the mitochondria-targeted antioxidant Mito-Q on oocyte development and unravel the role of Mito-Q in mitochondrial ATP production and thermogenesis regulation. Our results showed that Mito-Q had a positive effect on porcine oocytes maturation and subsequent embryo development. During oocytes IVM, Mito-Q could reduce ATP levels and ROS, increase lipid droplets accumulation, induce autophagy, and maintain mitochondrial temperature stability. Moreover, in metaphase II (MII) oocytes, Mito-Q would induce mitochondrial uncoupling manifested by decreased ATP, attenuated mitochondrial membrane potential (MMP), and increased mitochondrial thermogenesis. Notably, the expression of mitochondrial uncoupling protein (UCP2) was significantly reduced in oocytes treated with Mito-Q. Further study indicated that specific depletion of UCP2 in oocytes also resulted in increased thermogenesis, decreased ATP and declined MMP, suggesting that UCP2 downregulation may participate in Mito-Q-induced mitochondrial uncoupling. In summary, our data demonstrate that Mito-Q promotes oocyte maturation in vitro and maintains the stability of mitochondrial thermogenesis by inhibiting UCP2 expression.
线粒体产热是细胞对周围应激的一种适应性反应。氧化应激是卵母细胞体外成熟（IVM）过程中常见的应激之一，可导致线粒体功能障碍。本研究旨在探讨线粒体靶向抗氧化剂Mito-Q对卵母细胞发育的影响，并阐明Mito-Q在线粒体ATP生成和产热调节中的作用。我们的结果表明，Mito-Q对猪卵母细胞成熟及随后的胚胎发育有积极作用。在卵母细胞IVM期间，Mito-Q可降低ATP水平和活性氧（ROS），增加脂滴积累，诱导自噬，并维持线粒体温度稳定性。此外，在中期II（MII）卵母细胞中，Mito-Q会诱导线粒体解偶联，表现为ATP减少、线粒体膜电位（MMP）减弱和线粒体产热增加。值得注意的是，用Mito-Q处理的卵母细胞中线粒体解偶联蛋白（UCP2）的表达显著降低。进一步研究表明，卵母细胞中UCP2的特异性缺失也导致产热增加、ATP减少和MMP下降，表明UCP2下调可能参与Mito-Q诱导的线粒体解偶联。总之，我们的数据表明，Mito-Q通过抑制UCP2表达促进卵母细胞体外成熟并维持线粒体产热的稳定性。
