biostudies-literatureHarasimov KEuropean Research CouncilDeutsche Forschungsgemeinschaft (German Research Foundation)1124-1138https://www.ebi.ac.uk/biostudies/studies/S-EPMC11252011biostudies-literatureUnknown26(7)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 andNature cell biologyThe maintenance of oocytes in the mammalian ovary involves extreme protein longevity.PMC11252011SCHU 3047/1-1945528ERC-StG 945528 IMAP469281184Stutzer ASaha DGorry RLTaylor Tavares ALUrlaub HRaabe MRizzoli SOLiepe JCheng SFrombach ASWelp LMHaag SSchipper VTakaoka KHorokhovskyi YGrewe KPenir SMSchuh MHarasimov KfalseThe maintenance of oocytes in the mammalian ovary involves extreme protein longevity.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 and2024-01-01T00:00:00Z2024 Jul2025-04-26T08:05:40.909Z2025-04-06T12:33:16.558ZS-EPMC112520113890242310.1038/s41556-024-01442-7