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

Harasimov, Katarina; Gorry, Rebecca L.; Welp, Luisa M.; Penir, Sarah Mae; Horokhovskyi, Yehor; Cheng, Shiya; Takaoka, Katsuyoshi; Stützer, 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

doi:10.1038/s41556-024-01442-7

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学術論文

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

MPS-Authors

/persons/resource/persons217935

Harasimov, Katarina
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons299397

Gorry, Rebecca L.
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons256263

Welp, Luisa M.
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons243175

Penir, Sarah Mae
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons273425

Horokhovskyi, Yehor
Research Group of Quantitative and Systems Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons238086

Cheng, Shiya
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons204665

Takaoka, Katsuyoshi
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons299399

Stützer, Alexandra
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons242509

Frombach, Ann-Sophie
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons15676

Raabe, Monika
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons299404

Haag, Sara
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons299406

Saha, Debojit
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons299408

Schipper, Vera
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons15947

Urlaub, Henning
Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons208298

Liepe, Juliane
Research Group of Quantitative and Systems Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

/persons/resource/persons188399

Schuh, Melina
Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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引用

Harasimov, K., Gorry, R. L., Welp, L. M., Penir, S. M., Horokhovskyi, Y., Cheng, S., Takaoka, K., Stützer, A., Frombach, A.-S., Taylor Tavares, A. L., Raabe, M., Haag, S., Saha, D., Grewe, K., Schipper, V., Rizzoli, S. O., Urlaub, H., Liepe, J., & Schuh, M. (2024). The maintenance of oocytes in the mammalian ovary involves extreme protein longevity. Nature Cell Biology. doi:10.1038/s41556-024-01442-7.

引用: https://hdl.handle.net/21.11116/0000-000F-78FA-1

要旨

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.