德国马克斯-普朗克多学科科学研究所Melina Schuh、Juliane Liepe和Henning Urlaub研究团队合作取得一项新突破。他们发现哺乳动物卵巢中卵母细胞的维持与蛋白质的极端寿命有关。这一研究成果发表在2024年6月20日出版的国际学术期刊《自然-细胞生物学》上。

研究人员发现卵母细胞和卵巢蛋白稳态与蛋白质的极长寿命有关。与包括大脑在内的其他组织相比，小鼠卵巢具有更多的极长寿命蛋白质。这些长寿命蛋白质具有多种功能，包括在线粒体、细胞骨架、染色质和蛋白稳态中发挥功能。这些稳定的蛋白质不仅存在于卵母细胞中，也存在于长寿命的卵巢体细胞中。研究数据表明，哺乳动物通过伴侣蛋白和细胞抗氧化因子提高蛋白质的寿命并增强蛋白质稳态，从而维持雌性生殖细胞的活性。实际上，卵母细胞中的蛋白质聚集并没有随年龄的增长而增加，蛋白酶体的活性也没有衰减。

然而，延长蛋白质的寿命并不能完全阻止雌性生殖细胞的衰老。对约8890个蛋白质进行的大规模蛋白质组图谱分析表明，在衰老卵巢中，蛋白质稳态网络中许多长寿蛋白质会减少，同时伴随着大规模的蛋白质组重塑，这最终导致女性生育能力的下降。

据介绍，女性卵母细胞是与生俱来的。卵母细胞蛋白质组必须在妇女的整个生育期甚至往后数十年中维持最小损伤。

附：英文原文

Title: The maintenance of oocytes in the mammalian ovary involves extreme protein longevity

Author: Harasimov, Katarina, Gorry, Rebecca L., Welp, Luisa M., Penir, Sarah Mae, Horokhovskyi, Yehor, Cheng, Shiya, Takaoka, Katsuyoshi, Sttzer, Alexandra, Frombach, Ann-Sophie, Taylor Tavares, Ana Lisa, Raabe, Monika, Haag, Sara, Saha, Debojit, Grewe, Katharina, Schipper, Vera, Rizzoli, Silvio O., Urlaub, Henning, Liepe, Juliane, Schuh, Melina

Issue&Volume: 2024-06-20

Abstract: Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline.

DOI: 10.1038/s41556-024-01442-7

Source: https://www.nature.com/articles/s41556-024-01442-7