2024年新着論文 35　発生生物学分野から論文が発表されました

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

Nat Cell Biol. 2024 Jul;26(7):1124-1138. doi: 10.1038/s41556-024-01442-7. Epub 2024 Jun 20.

Authors

Katarina Harasimov^#^1 2, Rebecca L Gorry^#¹, Luisa M Welp^#^3 4, Sarah Mae Penir^#¹, Yehor Horokhovskyi^#⁵, Shiya Cheng¹, Katsuyoshi Takaoka^1 6, Alexandra Stützer³, Ann-Sophie Frombach¹, Ana Lisa Taylor Tavares^7 8, Monika Raabe³, Sara Haag^1 9, Debojit Saha¹, Katharina Grewe^10 11, Vera Schipper¹, Silvio O Rizzoli^10 11, Henning Urlaub^{12 13 14}, Juliane Liepe¹⁵, Melina Schuh^16 17

Affiliations

¹ Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
² Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
³ Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
⁴ Bioanalytics Group, Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
⁵ Quantitative and Systems Biology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
⁶ Laboratory of Embryology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
⁷ Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
⁸ East Anglian Medical Genetics Service, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, UK.
⁹ Translation Alliance Lower Saxony, Hannover, Braunschweig, Göttingen, Germany.
¹⁰ Department for Neuro and Sensory Physiology, University Medical Center Göttingen, Göttingen, Germany.
¹¹ Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany.
¹² Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. henning.urlaub@mpinat.mpg.de.
¹³ Bioanalytics Group, Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany. henning.urlaub@mpinat.mpg.de.
¹⁴ Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells, University of Göttingen, Göttingen, Germany. henning.urlaub@mpinat.mpg.de.
¹⁵ Quantitative and Systems Biology Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. juliane.liepe@mpinat.mpg.de.
¹⁶ Department of Meiosis, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. melina.schuh@mpinat.mpg.de.
¹⁷ Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells, University of Göttingen, Göttingen, Germany. melina.schuh@mpinat.mpg.de.

^# Contributed equally.

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.

Conflict of interest statement

The authors declare no competing interests.

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