Mitochondrial dysfunction plays a crucial role in the pathological physiology of polycystic ovary syndrome (PCOS). Mitochondrial quality control system is vital to maintaining mitochondrial function, includes mitochondrial biosynthesis, dynamics and mitophagy. While mitophagy as a specific autophagy, plays an important role in the mitochondrial quality control system and is mediated by some signaling pathways to eliminate the excessive production of reactive oxygen species (ROS), such as hypoxia-inducible factor (HIF)-1α/B-cell lymphoma-2 adenovirus E1B 19 kDa interacting protein 3 (BNIP3). Our previous studies have found that excessive production of ROS and the decreased expression of HIF-1α in the ovaries of PCOS rats. Thus, we hypothesized that excessive ROS leads to mitochondrial dysfunction, attenuates HIF-1α/BNIP3-mediated mitophagy in the ovaries of PCOS rats, and further reduces the mitophagic defense. Firstly, the oxidative stress status was detected and found excessive ROS damages ovarian tissue in PCOS rats. Secondly, the marker proteins of mitochondrial biosynthesis/dynamics and amount were examined and found that their expression levels were abnormal, which showed that the abnormal mitochondrial quality control system leads to accumulate the excess or damaged mitochondria in PCOS ovaries. Finally, we detected the HIF-1α/BNIP3 pathway and found HIF-1α-mediated mitophagy is impaired in the ovaries of PCOS rats. Together, these results clearly demonstrated excessive ROS causes mitochondrial dysfunction via the abnormal mitochondrial quality control system, and attenuates HIF-1α/BNIP3-mediated mitophagic defense in the granulosa cells of PCOS rats, which will provide a new direction for further understanding the role of HIF-1α in the molecular mechanism of mitochondrial dysfunction in PCOS ovaries.

线粒体功能障碍在多囊卵巢综合征（PCOS）的病理生理学中起着至关重要的作用。线粒体质量控制系统对于维持线粒体功能至关重要，包括线粒体生物合成、动力学和线粒体自噬。而线粒体自噬作为一种特异性自噬，在线粒体质量控制系统中发挥着重要作用，并由一些信号通路介导以消除活性氧（ROS）的过度产生，如缺氧诱导因子（HIF）-1α/B -细胞淋巴瘤 2 腺病毒 E1B 19 kDa 相互作用蛋白 3 (BNIP3)。我们之前的研究发现PCOS大鼠卵巢中ROS的过量产生和HIF-1α的表达降低。因此，我们假设过量的 ROS 会导致线粒体功能障碍，减弱 PCOS 大鼠卵巢中 HIF-1α/BNIP3 介导的线粒体自噬，并进一步降低线粒体自噬防御。首先，检测氧化应激状态，发现过量的ROS损伤PCOS大鼠的卵巢组织。其次，检测线粒体生物合成/动力学和数量的标志蛋白，发现其表达水平异常，说明线粒体质控系统异常导致PCOS卵巢中线粒体积累过多或受损。最后，我们检测了 HIF-1α/BNIP3 通路，发现 HIF-1α 介导的线粒体自噬在 PCOS 大鼠的卵巢中受损。总之，这些结果清楚地表明，过量的 ROS 通过异常的线粒体质量控制系统导致线粒体功能障碍，