Xie Yuan, Chen Shuwen, Guo Zaixin, Tian Ying, Hong Xinyu, Feng Penghui, Xie Qiu, Yu Qi
Department of Obstetrics and Gynecology National Clinical Research Center for Obstetric & Gynecologic Diseases State Key Laboratory for Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Peking Union Medical College Hospital (Dongdan Campus) Beijing China.
Department of Medical Research Center State Key Laboratory for Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China.
MedComm (2020). 2023 Oct 9;4(5):e396. doi: 10.1002/mco2.396. eCollection 2023 Oct.
Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post-translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography-tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS-like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down-regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.
多囊卵巢综合征（PCOS）是一种常见的生殖内分泌疾病，伴有代谢异常和排卵障碍。翻译后修饰（PTMs）具有功能相关性，并加强了代谢与细胞功能之间的联系。赖氨酸巴豆酰化是一种新发现的翻译后修饰，其在PCOS中的功能尚未见报道。为了探究巴豆酰化参与PCOS代谢稳态异常和卵母细胞成熟的分子机制，我们利用液相色谱-串联质谱分析，构建了由脱氢表雄酮诱导建立的PCOS样小鼠模型卵巢组织中巴豆酰化修饰的综合图谱。与对照样本相比，PCOS卵巢中参与代谢过程的蛋白质的巴豆酰化水平显著降低。进一步研究表明，赖氨酸390处的Lon蛋白酶1（LONP1）去巴豆酰化与PCOS中的线粒体功能障碍有关。此外，PCOS中LONP1的巴豆酰化水平与卵巢组织氧化应激水平、雄激素水平和卵母细胞发育相关。同样，在PCOS患者的血液样本中也观察到LONP1及其巴豆酰化水平的下调。总的来说，我们的研究揭示了一种机制，即LONP1的去巴豆酰化可能减弱其活性并改变卵泡微环境，从而影响PCOS中的卵母细胞成熟。
