Mitochondrial Function Regulated by Mitoguardin-1/2 Is Crucial for Ovarian Endocrine Functions and Ovulation
Mitochondrial Function Regulated by Mitoguardin-1/2 Is Crucial for Ovarian Endocrine Functions and Ovulation
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Mitoguardin-1/2 调节的线粒体功能对于卵巢内分泌功能和排卵至关重要
DOI：
10.1210/en.2017-00487
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发表时间：
2017-11-01
期刊：
影响因子：
4.8
通讯作者：
Fan, Heng-Yu
中科院分区：
文献类型：
--
作者：
Liu, Xiao-Man;Zhang, Yin-Li;Fan, Heng-Yu
线粒体动态变化、线粒体形态和线粒体数量的平衡对于细胞代谢至关重要。一旦受到干扰，这些过程的紊乱通常会导致动物患病甚至死亡。我们在果蝇中进行了大规模的基因筛查，发现了编码线粒体外膜蛋白的线粒体卫士基因 (Miga)。为了检查其哺乳动物同源物 Miga1 和 Miga2 的生理功能，我们产生了 Miga1 和 Miga2 单敲除和双敲除小鼠品系，发现敲除小鼠能够存活，但雌性生育力低下。这些小鼠的卵巢表型表明 MIGA1/2 蛋白在排卵和卵巢类固醇生成中发挥重要作用。 Miga1/2 敲除颗粒细胞的体内和体外分析显示，黄体化和类固醇生成存在严重缺陷，并且线粒体形态和功能对促性腺激素的反应紊乱。这是一份有关排卵和黄体化过程中线粒体融合和形态调节线粒体功能的基因的报告。这些结果揭示了促性腺激素调节卵巢内分泌功能的机制，并为不孕女性的治疗提供了线索。
The balances of mitochondrial dynamic changes, mitochondrial morphology, and mitochondrial number are critical in cell metabolism. Once they are disturbed, disorders in these processes generally cause diseases or even death in animals. We performed large-scale genetic screenings in fruit flies and discovered the mitoguardin gene (Miga) that encodes for a mitochondrial outer membrane protein. To examine the physiological functions of its mammalian homologs Miga1 and Miga2, we generated Miga1 and Miga2 single- and double-knockout mouse strains and found that the knockout mice were viable, but the females were subfertile. The ovarian phenotypes of these mice suggested that the MIGA1/2 proteins play an important role in ovulation and ovarian steroidogenesis. In vivo and in vitro analyses of Miga1/2-knockout granulosa cells showed severe defects in luteinization and steroidogenesis and disordered mitochondrial morphology and function in response to gonadotropins. This is a report of genes involved in mitochondrial fusion and morphology-regulating mitochondrial functions during ovulation and luteinization. These results suggest a mechanism of gonadotropin-regulated ovarian endocrine functions and provide clues for therapeutic treatments of infertile females.